JPH06102647B2 - Method and apparatus for granulating cysteamine hydrochloride - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and apparatus for granulating cysteamine hydrochloride. More specifically, the present invention relates to a granulation method and apparatus for siateamine hydrochloride without corrosion of the apparatus.

[0002]

2. Description of the Related Art Conventionally, cisamine hydrochloride is generally produced as follows.

(1) A method for producing cysteamine from etileimine and hydrogen sulfide and producing cysteamine hydrochloride using hydrogen chloride, (2) a method for producing cysteamine hydrochloride by adding hydrochloric acid to 2-dimethyl-thiazolidine (Japanese Patent Publication No. 50-29,444), (3) A method of producing cysteamine hydrochloride using monoethanolamine as a starting material (Japanese Patent Laid-Open Nos. 57-88,171 and 57-57).
-144,252, JP-B-55-17,019, JP-A-57-64,684, JP-A-57-53,458.
JP-A-57-67,555, JP-A-57-64,
No. 661) etc.

[0004] Conventionally, cysteamine hydrochloride is generally handled in the form of powder. However, cysteamine hydrochloride itself is irritating to the human body, and when fine powder is inhaled, it stimulates the nasal cavity and pharynx, coughs,
It has unfavorable properties such as sneezing and inflammation if left on the skin. Therefore, when handling powdery cysteamine hydrochloride containing a large amount of such fine powder, it is necessary to take strict care to avoid contact with the skin as much as possible.

Further, the powdery cysteamine hydrochloride is preferably agglomerated with time in the container during storage, and it cannot be taken out of the container before use, or even if taken out, However, it also has a problem that it cannot be used unless it is crushed. In addition, the cysteamine hydrochloride, which has been lumped, has a problem that it takes a long time to dissolve.

[0006] Thus, it must be said that powdered cysteamine hydrochloride is a very problematic product form.

[0007]

As described above, the existing powdery form of cysteamine hydrochloride has many problems, and causes various inconveniences especially when it is handled industrially in large quantities. Therefore, the present inventors have reduced the generation of fine powder by melting such cysteamine hydrochloride, and then cooling and solidifying by using an on-plate dropping granulator to granulate, and further, during storage. It was also found that a stable product form for a long period of time can be obtained without agglomeration (Japanese Patent Publication No. 1-240,169). In this case, cooling is usually performed with a metal plate such as stainless steel in terms of heat transfer effect. However, since cysteamine hydrochloride has a strong corrosive property, there is a problem that a metal component is mixed into the granulated product and the granulated product is colored.

Accordingly, it is an object of the present invention to provide a new granulation method for cysteamine hydrochloride and an apparatus therefor. Another object of the present invention is that the generation of fine powder is small, the particle size is well aligned, it does not agglomerate even during storage, it is extremely easy to handle, and the granulated product is colored by mixing metal components. It is intended to provide a method for granulating cysteamine hydrochloride and an apparatus therefor capable of preventing the occurrence of cystamine.

[0009]

Means for Solving the Problems The above-mentioned various objects are obtained by cooling and solidifying a cysteamine hydrochloride melt using a plate-shaped dropping type granulator to granulate the plate-shaped dropping type granulator. The cysteamine hydrochloride granulation method is characterized in that the cooling substrate is dropped onto a metal substrate formed by coating the surface of the cooling resin with a fluororesin, followed by cooling and solidification.

Further, these various purposes are represented by the general formula (1) in the presence of water.

[0011]

[Chemical 2]

(Wherein R ¹ and R ² each independently represents at least one alkyl group selected from the group consisting of alkyl groups having 1 to 2 carbon atoms).
After adding an equivalent amount or more of hydrochloric acid to the dialkylthiazolines and sequentially distilling off the dialkylketone produced as a by-product, the temperature is raised to 130 to 160 ° C. to complete the reaction, and then 68 to 160. It can also be achieved by a granulation method of cysteamine hydrochloride, which comprises cooling and solidifying a molten cysteamine hydrochloride obtained by dehydration under reduced pressure while maintaining the temperature at 0 ° C. using a plate-shaped dropping granulator.

These various objects are composed of a cysteamine hydrochloride dropping device, an endless transfer device provided under the dropping device, and a cooling device provided under a cooling substrate of the transfer device. This can also be achieved by a cysteamine hydrochloride granulating apparatus, which is a metal substrate in which the surface of the substrate of the transfer device is coated with a fluororesin.

[0014]

Next, an embodiment of the present invention will be described with reference to the drawings.

FIG. 1 is a schematic sectional view of an apparatus for carrying out the method of the present invention. That is, in the granulation chamber 2 provided in the building 1, there is provided a conveyor device 3, for example, a belt conveyor including rolls 4, 5 and an endless belt 6, and a cooling medium spray is provided on the lower surface of the endless belt 6. A device 7 is provided. A cooling medium recovery device 8 is provided below the spray device 7. A conduit 10 from a cooling device 9 is connected to the spraying device 7 via a pump 11, while a conduit 12 is connected to the recovery device 8 and is connected to the cooling device 9. A cooling medium such as brine is supplied to the cooling device 9 through the conduit 13 and is maintained at a predetermined temperature.

A molten cysteamine hydrochloride dripping device 14 is provided at the upper part of the conveying device 3 and in the front part in the traveling direction, and a conduit 15 from the cysteamine hydrochloride melting device (not shown) is provided in the dripping device 14. It is connected.

A hopper 16 is connected to the lower part of the granulating chamber 2 and the downstream end of the conveying device in the traveling direction. Further, conduits 17 and 18 connected to a dehumidifier (not shown) are connected to the inside of the building 1 and the hopper 16 via a pump 19, while an exhaust conduit 20 is connected to the opposite side of the building 1. .

The endless belt 6 is made of metal such as stainless steel, aluminum and copper, and its surface is coated with fluororesin. As the method for coating the fluororesin, there are usually a baking method, a room temperature drying spray method, a fluororesin sticking method with an adhesive, and the like. As the fluororesin, there are polytetrafluoroethylene, tetrafluoroethylene-hexafluoropropylene copolymer, polyvinylidene fluoride, polyvinyl fluoride, tetrafluoroethylene-perfluorovinyl ether copolymer and the like, but preferably polytetrafluoroethylene. It is fluoroethylene.

Next, a method for granulating cysteamine hydrochloride using such an apparatus will be described. First, the cysteamine hydrochloride melted by a melting device (not shown),
It is supplied to the drip device 14 by a conduit 15 which is kept warm if necessary, and drops 21 are dropped on the belt conveyor 6, and while the belt conveyor 6 runs, the cooling medium spraying device 7 directs the lower surface of the belt conveyor 6. A cooling medium, such as water or a polyhydric alcohol-containing liquid, is sprayed, and the droplets 21 are cooled, solidified, and shaped. The sprayed cooling medium is recovered by the recovery device 8. As this recovery device,
There are various shapes, but usually a tray shape. The recovered cooling medium 22 is sent to the cooling device 9 through the conduit 12 to be cooled to a constant temperature, and then is sent to the cooling medium spraying device 7 through the conduit 10 via the pump 11.

The granulated material thus formed is scraped off by the scraper 32 and discharged by the hopper 16. If necessary, dry air is introduced into the building 1 and the hopper 16 from the conduits 17 and 18, and is discharged from the exhaust conduit 20 to keep the building 1 and the hopper 16 in a dry state.

The cooling medium used in the present invention includes water, polyhydric alcohol and the like. However, since cysteamine hydrochloride itself has a very high hygroscopic property, a polyhydric alcohol-containing liquid is preferable. As the polyhydric alcohol-containing liquid, for example, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, glycerin, butanediol, neopentyl glycol, pentaerythritol or the like alone or There is a mixture or an aqueous solution thereof, but ethylene glycol, diethylene glycol, propylene glycol and the like are preferable, and ethylene glycol is most preferable.

When a polyhydric alcohol-containing liquid is used as the cooling medium, the polyhydric alcohol-containing liquid supplied to the cooling medium spraying device absorbs water in the atmosphere gas in the granulating device, and therefore the granulating device is used. The inside is always kept dry,
The polyhydric alcohol-containing liquid that has absorbed moisture and has reached a predetermined concentration or less is discharged from the discharge port 23, and as much as that, the supply port 24.
A new polyhydric alcohol-containing liquid is supplied.

There are various types of dropping devices 14, and for example, as shown in FIG. 2, for example, as shown in FIG. 2, a porous outer cylinder 25 is rotatable around a fixed inner cylinder 24 on the same axis. The molten cysteamine hydrochloride is supplied by the conduit 15 to the liquid reservoir 26 formed near the central axis of the inner cylinder 24, and is dripped onto the conveyor belt 6 from the slit 27 provided in the lower portion of the inner cylinder 24. To be done. In this case, the molten liquid is dropped when the hole of the outer cylinder 25 is aligned with the slit 27, and is not dropped when the holes other than the hole pass.

Further, as shown in FIG. 3, the dropping member main body 2
It is also possible to form a hollow portion in which the piston 29 is fitted in 8 and to make the conduit 15 communicate with this, and reciprocate the piston 29 to drop the hollow portion on the belt conveyor 6 from the lower hole 31.

By heating to 68 ° C. or higher, preferably 70 to 100 ° C., molten cysteamine hydrochloride is obtained, and this is dropped onto a substrate cooled to 65 ° C. or lower, preferably 15 to 40 ° C. and cooled. The granular cysteamine hydrochloride is obtained by solidifying.

Further, another embodiment of the present invention will be described.

First, 2-dialkylthiazolines represented by the general formula (1), for example, 2-dimethylthiazoline,
2-Dialkylthiazolines such as 2-methyl-ethylthiazoline and 2-diethylthiazoline and water are put in a reaction apparatus and the liquid temperature is 20 to 60 ° C. under stirring, preferably 4
While maintaining the temperature at 0 to 60 ° C, hydrochloric acid having a concentration of 5 to 40% by weight, preferably 20 to 38% by weight is added dropwise to adjust the pH of the reaction solution to 1 to 7, preferably 2.5 to 3.5. Next, the dialkyl ketone produced as a by-product during the reaction is sequentially and continuously distilled out of the reaction system, and the liquid temperature is raised to 130 to 160 ° C., preferably 140 to 150 ° C. at atmospheric pressure for about 10 hours. , 50 Torr or less, preferably 30 Torr or less, and dehydration is performed to obtain a molten cysteamine hydrochloride.

The molten cysteamine hydrochloride obtained was mixed with 70
The molten cysteamine hydrochloride can be granulated by cooling to -100 ° C and using the granulating apparatus shown in Figs.

That is, while maintaining the molten cysteamine hydrochloride in the conduit 15 at a temperature of 70 to 100 ° C., preferably 70 to 90 ° C., 15 to 40 from the dropping device 14 shown in FIG.
C., preferably maintained at a temperature of 20 to 30.degree. C., and dropped on a stainless steel belt conveyor 6 whose surface is coated with a fluororesin, for example, polytetrafluoroethylene or the like, cooled, solidified and averaged. Granules having a particle size of 1 to 15 mm can be obtained. During this time, the belt conveyor 6
The lower surface is cooled by spraying ethylene glycol sent from the cooling device 9 via a pump from the cooling medium spraying device 7. The sprayed ethylene glycol is recovered by the recovery device 8 and then returned to the cooling device 9 to be cooled to a predetermined temperature. Dry air is supplied into the building 1 and the hopper 16 from the conduits 17 and 18, and the relative humidity thereof is 40% or less, preferably 30%.
Kept below%. The obtained granular material is collected in the hopper 16.

[0030]

EXAMPLES Next, the present invention will be described in more detail with reference to examples.

Example 1 Powdered cysteamine hydrochloride was granulated using the granulating apparatus shown in FIGS. That is, powdery cysteamine hydrochloride is melted at a temperature of 80 ° C. by a melting device (not shown),
The temperature was maintained at 25 ° C. by a dropping device 14 shown in FIG. 2 via a conduit 15 which was kept warm while maintaining the temperature at about this temperature, and the surface was made of stainless steel coated with polytetrafluoroethylene to a film thickness of 10 μm. It was dropped onto the belt conveyor 6 and cooled and solidified to obtain granules having an average particle diameter of 5 mm. During this time, the lower surface of the belt conveyor 6 is cooled by causing the cooling medium spraying device 7 to spray the ethylene glycol sent from the cooling device 9 via the pump. The sprayed ethylene glycol was recovered by the recovery device 8 and then returned to the cooling device 9 to be cooled to a predetermined temperature. In addition, inside the building 1 and hopper 1
Dry air was supplied to the inside of No. 6 through conduits 17 and 18, and its relative humidity was kept at 30%. Granules are in hopper 1
However, the water content in the granules was 0.1% by weight. Further, the iron content in the granulated product was 1 ppm or less, and coloring was not recognized.

Comparative Example 1 A granulated product having an average particle size of 5 mm was obtained in the same manner as in Example 1 except that a belt conveyor made of stainless steel whose surface was not coated was used. in this case,
The iron content in the granulated product was 5 ppm and colored.

Example 2 420 g of water and 1170 g of 2-dimethylthiazoline were placed in a glass-lined reactor equipped with a stirrer, a thermometer and a condenser, and 38% by weight while maintaining the liquid temperature under stirring at 40-60 ° C. Hydrochloric acid was added dropwise over about 2 hours to adjust the pH of the reaction solution to 3.0. Next, the dialkyl ketone produced as a by-product during the reaction was successively and continuously distilled out of the reaction system, and the liquid temperature was raised to 150 ° C. over about 10 hours at normal pressure, and 3
The pressure was reduced to 0 Torr or less, and this pressure was maintained for 3 hours for dehydration.

The obtained molten cysteamine hydrochloride was added to 80
The temperature is kept at 25 ° C. by the dropping device 14 shown in FIG. 2 while keeping the temperature at 80 ° C. in the conduit 15 shown in FIG. 2, and the surface is coated with polytetrafluoroethylene having a film thickness of 10 μm. It was dripped on the stainless steel belt conveyor 6 thus prepared, cooled and solidified to obtain a granular material having an average particle diameter of 5 mm. During this time, the lower surface of the belt conveyor 6 is cooled by causing the cooling medium spraying device 7 to spray the ethylene glycol sent from the cooling device 9 via the pump. The sprayed ethylene glycol was recovered by the recovery device 8 and then returned to the cooling device 9 to be cooled to a predetermined temperature. Dry air was supplied into the building 1 and the hopper 16 through the conduits 17 and 18, and the relative humidity thereof was maintained at 30%. Granules are
Although recovered in the hopper 16, the water content in the granular material was 0.1% by weight. The iron content in the granulated product is 1
It was below ppm and no coloring was observed.

[0035]

EFFECTS OF THE INVENTION Since the present invention has the above-mentioned constitution, it not only does not cause irritation to the human body, especially the nasal cavity, pharynx, etc., and skin illness due to powder inhalation, and fluorine Since it is coated with a resin, it is possible to obtain a granulated product that is excellent in corrosion resistance and does not contain metal. Further, if the spray cooling of the substrate is carried out with the polyhydric alcohol-containing liquid, there is an advantage that the obtained granulated product does not substantially absorb moisture.

[Brief description of drawings]

FIG. 1 is a schematic sectional view showing an embodiment of a granulating apparatus according to the present invention,

FIG. 2 is a schematic sectional view showing an embodiment of a dropping device in the granulating device,

FIG. 3 is a schematic sectional view showing another embodiment of the dropping device.

[Short description of reference numerals] 1 ... Building, 2 ... Granulation chamber, 3 ... Conveying device, 6 ... Belt conveyor, 7 ... Cooling medium spraying device,
8 ... Cooling medium recovery device, 9 ... Cooling device, 14 ... Dropping device, 15 ... Conduit.

Claims (5)

[Claims] 1. When a cysteamine hydrochloride melt is cooled and solidified by using a plate-shaped dropping granulator to granulate, the surface of a cooling substrate of the plate-shaped dropping granulator is coated with a fluororesin. A method for granulating cysteamine hydrochloride, which comprises dropping and cooling and solidifying the resulting metal substrate. 2. A compound represented by the general formula (1): (In the formula, R ¹ and R ² are each independently a carbon number of 1 to
At least one alkyl group selected from the group consisting of 2 alkyl groups is shown. 13) while adding an equivalent amount or more of hydrochloric acid to the 2-dialkylthiazoline represented by the formula (1) and distilling the by-produced dialkylketone successively and continuously out of the reaction system.
After the temperature is raised to 0 to 160 ° C. to complete the reaction, 68 to
While maintaining at 160 ° C., the molten cysteamine hydrochloride obtained by dehydration under reduced pressure was cooled using a plate-shaped dropping granulator,
A method for granulating cysteamine hydrochloride, which comprises coagulating. 3. A metal obtained by coating the surface of a cooling substrate of the plate-shaped dropping granulator with a fluororesin when the molten cysteamine hydrochloride is cooled and solidified by using the plate-shaped dropping granulator. The cysteamine hydrochloride granulation method according to claim 2, wherein the cysteamine hydrochloride is dropped onto a substrate for cooling and solidification. 4. An apparatus for dropping molten cysteamine hydrochloride,
The endless transfer device is provided below the dropping device, and the cooling device is provided below the cooling substrate of the transfer device, and the surface of the substrate of the transfer device is covered with a fluororesin. A cysteamine hydrochloride granulator that consists of a substrate. 5. Obtained by melting cysteamine hydrochloride
The melt is cooled and solidified using a plate-shaped dropping granulator.
When granulating, cooling of the cooling substrate of the plate-shaped dropping granulator
Spray a liquid containing polyhydric alcohol on the lower surface of the substrate.
Of cysteamine hydrochloride, which is characterized by
Granulation method.