Method for producing gelatin particles and gelatin particle production apparatus

Abstract

To sort gelatin grains having high safety, and a desired grain size.SOLUTION: A production method of gelatin grains having a granulation step of spraying, drying and granulating liquid gelatin includes steps of: a first sorting step of sorting gelatin grains G obtained in the granulation step with a first sieve 11a with a first opening; a pulverization step of pulverizing gelatin grains G1 which do not pass through the first sieve 11a in the first sorting step; a second sorting step of sorting gelatin grains G2 pulverized in the pulverization step with the first sieve; a third sorting step of sorting gelatin grains g, g1 which pass through the first sieve in the first sorting step and the second sorting step with a second sieve 12a with a second opening smaller than the first opening; a recovery step of recovering gelatin grains g2 which do not pass through the second sieve 12a in the third sorting step; and a heating step of subjecting the recovered gelatin grains g2 to heating treatment.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention relates to a method for producing gelatin particles and an apparatus for producing gelatin particles, and more particularly to a method for producing gelatin particles by spraying and drying liquid gelatin to granulate the same and an apparatus for producing gelatin particles.

Background Art

[0002] Conventionally, gelatin has been used in fields such as food and industry, and granulated gelatin particles are used as a form of its use. As a method for producing such gelatin particles, there are known a spray drying method (Patent Document 1) in which liquid gelatin is sprayed and dried, and an emulsion method (Patent Document 2) in which gelatin droplets are discharged into a hydrophobic solvent, the hydrophobic solvent is dehydrated and washed, and then dried.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] Here, the gelatin particles as described above are also used in the medical field. For example, they are used as a sustained-release carrier in which a medicinal ingredient is impregnated into the gelatin particles and the ingredient is gradually released in the body, or as a culture substrate interposed between each sheet when a plurality of cell sheets such as myocardial sheets are stacked and used. As such medical gelatin particles, those having a particle size of about several tens of μm are required from the viewpoints of operability and affinity with cells. However, when the method described in Patent Document 1 is used, the particle size is as large as 250 to 350 μm, which is inappropriate. On the one hand, according to the method described in Patent Document 2, although the particle size can be reduced, since highly toxic acetone or the like is used as the solvent for dehydration and drying, there is a problem with safety when using the obtained gelatin particles for medical use. In view of such problems, the present invention provides a method for producing gelatin particles and a device for producing gelatin particles that are highly safe and can obtain gelatin particles having a desired particle size.

Means for Solving the Problems

[0005] That is, the method for producing gelatin particles according to the invention of claim 1 has a granulation step of spraying and drying liquid gelatin to granulate it, and recovering the granulated gelatin particles as gelatin particles within a range consisting of the upper and lower limit values of several tens of μm desired. In the method for producing gelatin particles, the gelatin particles obtained by the above granulation step are sieved with a first mesh size for selecting gelatin particles below the upper limit value of the desired range. Selected in the range of 90 to 45 μm a first screening step of screening with a first sieve; a pulverization step of pulverizing the gelatin particles exceeding the upper limit value of the desired range that did not pass through the first sieve in the above first screening step; a second screening step of screening the gelatin particles pulverized in the pulverization step with the first sieve; the gelatin particles that passed through the first sieve in the above first screening step and second screening step are sieved with a second mesh size for selecting gelatin particles below the lower limit value of the desired range smaller than the above first mesh size. Selected in the range of 40 to 10 μm a third screening step of screening with a second sieve; a recovery step of recovering the gelatin particles exceeding the lower limit value of the desired range that did not pass through the second sieve in the above third screening step; and a heating step of heat-treating the recovered gelatin particles. Also Claim 4 The gelatin particle production apparatus according to the invention of, is provided with granulation means for spraying and drying liquid gelatin to granulate it, and in the gelatin particle production apparatus for recovering the granulated gelatin particles as gelatin particles within a range consisting of the upper and lower limit values of several tens of μm desired. A first aperture for screening gelatin particles having a size equal to or less than the upper limit of a desired range Selected in the range of 90 to 45 μm A first screening means having a first sieve, and a second aperture for screening gelatin particles having a size equal to or less than the lower limit of a desired range smaller than the first aperture Selected in the range of 40 to 10 μm A second screening means having a second sieve, a grinding means for grinding gelatin particles, and a heating means for heat-treating gelatin particles, are provided The first screening means screens the gelatin particles granulated by the granulating means, and the grinding means grinds the gelatin particles that did not pass through the first sieve Furthermore, the first screening means screens the gelatin particles ground by the grinding means The second screening means screens the gelatin particles that were screened by the first screening means and passed through the first sieve It is characterized in that gelatin particles that did not pass through the second sieve by the screening by the second screening means are collected and heat-treated by the heating means

Advantages of the Invention

[0006] According to the above invention, for gelatin particles granulated by spraying and drying liquid gelatin and containing particles larger than a desired particle size, gelatin particles exceeding the desired particle size range are screened and ground by a first sieve, and for the ground gelatin particles, gelatin particles exceeding the desired particle size range are screened again by the first sieve. Therefore, compared with the case of directly screening gelatin particles in a desired particle size range from the granulated gelatin particles or directly grinding the granulated gelatin particles and screening gelatin particles in a desired particle size range, more gelatin particles in the desired particle size range can be recovered And since it is granulated by a spray drying method in which liquid gelatin is sprayed and dried, no toxic components remain and it can be safely used for medical purposes

Brief Description of the Drawings

[0007]

Figure 1

Figure 2

Figure 3

Mode for Carrying Out the Invention

[0008] The following describes the illustrated embodiments. FIG. 1 shows a gelatin particle manufacturing apparatus 1, which is an apparatus for obtaining gelatin particles having a particle size suitable for medical use. The gelatin particles for medical use manufactured in this embodiment can be used as a sustained-release carrier for impregnating a medicinal ingredient and gradually releasing the ingredient in the body, and also as a culture substrate to be interposed between each sheet when a plurality of cell sheets such as myocardial sheets are stacked and used, enabling various clinical applications. Here, when gelatin particles are used for medical purposes, it is desirable that the particle size be about several tens of μm from the viewpoints of operability and affinity with cells. The gelatin particle manufacturing apparatus 1 of this embodiment is for manufacturing such gelatin particles for medical use.

[0009] The gelatin particle manufacturing apparatus 1 of this embodiment includes a granulating means 2 for granulating gelatin particles, a sorting means 3 for sorting gelatin particles of a desired particle size from the granulated gelatin particles, a pulverizing means 4 for pulverizing gelatin particles larger than the desired particle size, and a heating means 5 for subjecting the sorted gelatin particles to vacuum heat treatment. The gelatin particle manufacturing apparatus 1 also includes a clean room 6 whose interior is maintained at a predetermined air cleanliness to form a clean space, and an isolator 7 that similarly forms a clean space with its interior maintained at a predetermined air cleanliness and can be maintained in a sterile state by decontaminating its interior. The granulating means 2, sorting means 3, and pulverizing means 4 are housed inside the clean room 6, and the isolator 7 is provided between the clean room 6 and the heating means 5. At one end of the above clean room 6, a carry-in door 6a for carrying in liquid gelatin or the like, which is a raw material for gelatin particles, is provided, and on the side surface, gloves 6g for workers to wear are provided.

[0010] Since the above granulation means 2 is a conventionally well-known one, detailed description thereof will be omitted. It includes a cylindrical processing cylinder 2a, a spraying means 2b provided at the lower part of the processing cylinder 2a for spraying liquid gelatin, and an air flow generating means having an air nozzle (not shown) for generating an air flow composed of dry air inside the processing cylinder 2a. The inside of the above processing cylinder 2a is set to a predetermined temperature. For example, the internal temperature of the processing cylinder 2a can be set to 70 to 150 °C. The above spraying means 2b is configured to spray liquid gelatin in which solid gelatin is dissolved in water in a mist form, and as this liquid gelatin, liquid gelatin dissolved at a concentration of 1 to 30 wt% can be used. Also, the spraying means 2b can spray the above liquid gelatin into the inside of the processing cylinder 2a at a rate of 0.5 to 10 g / min, and the above air flow generating means can inject dry air into the inside of the processing cylinder 2a at a rate of 20 to 100 L / min.

[0011] With such a configuration, the minute droplet-shaped liquid gelatin sprayed by the above spraying means 2b is dried while floating inside the processing cylinder 2a by the dry air supplied by the above air flow generating means, forming small seed particles. New liquid gelatin collides with this seed particle, and as the collided liquid gelatin dries, the particle size of the seed particle expands. Thereafter, by repeating the collision and drying of the liquid gelatin, gelatin particles are formed. Here, the method for granulating gelatin particles using such granulation means 2 is called a so-called spray drying method and is also described in the above Patent Document 1. Compared with the emulsion method described in Patent Document 2, since no drug is used, the obtained gelatin particles have high safety when used for medical purposes. However, when the spray drying method is used, as described in Patent Document 1, the most frequent particle size of the gelatin particles obtained is 250 to 350 μm, which is too large to be suitable for medical use. As will be described in detail below, the gelatin particles granulated by the granulation means 2 of this example also have an average particle size exceeding 100 μm.

[0012] The sorting means 3 includes two sorting means, a first sorting means 11 and a second sorting means 12. The first sorting means 11 has a first sieve 11a with a first mesh size, and the second sorting means 12 has a second sieve 12a with a second mesh size smaller than the first mesh size of the first sieve 11a. These first and second sorting means 11 and 12 each perform sorting of the input gelatin particles by means of fine vibrations caused by ultrasonic vibrations. That is, the first sorting means 11 and the second sorting means 12 include ultrasonic vibration means 11b and 12b for vibrating the first and second sieves 11a and 12a, and recovery containers 11c and 12c for recovering the gelatin particles that have passed through the first and second sieves 11a and 12a. The mesh sizes of the first and second sieves 11a and 12b can each be those having the mesh sizes defined in the ISO standard, and any desired ones can be used according to the particle size of the gelatin particles desired. When sorting gelatin particles with a particle size of several tens of μm for medical use, it is desirable to select the first mesh size of the first sieve 11a in the range of 90 to 45 μm, and the second mesh size of the second sieve 12a in the range of 40 to 10 μm.

[0013] A conventionally known configuration can be adopted for the pulverizing means 4. Inside, there is provided an injection means (not shown) for jet-injecting sterile air, and in addition, it is provided with a hopper 4a for introducing the gelatin particles before pulverization. With such a configuration, the injection means collides sterile air at high speed against the gelatin particles introduced by the hopper 4a, thereby pulverizing the gelatin particles.

[0014] In this embodiment, the granulating means 2, the sorting means 3 (the first sorting means 11 and the second sorting means 12), and the pulverizing means 4 are arranged such that the sorting means 3 is disposed between the granulating means 2 and the pulverizing means 4. Thereby, the workability when moving the gelatin particles from the granulating means 2 to the first sorting means 11, from the first sorting means 11 to the pulverizing means 4, from the pulverizing means 4 to the first sorting means 11, and from the first sorting means 11 to the second sorting means 12 is improved. The above arrangement is particularly effective when each means is disposed close to the inside of the clean room 6 and the gelatin particles are moved by an operation using the glove 6g. Note that, as long as the sorting means 3 is positioned between the granulating means 2 and the pulverizing means 4, it is not necessary to arrange them in a line, and each means may be laid out according to the shape and size of the clean room 6.

[0015] A conventionally known one can be used as the heating means 5, and by heating the accommodated gelatin particles at a required temperature under a vacuum state, a crosslinking reaction is caused in the gelatin particles. In addition, since the gelatin particles are sterilized by such a heat treatment, the gelatin particles after the heating by the heating means 5 are in a sterile state and can be used for treatment or the like in the state taken out from the heating means 5.

[0016] The isolator 7 includes a sterile air supply means (not shown) for supplying sterile air to the internal space and a decontamination means 13 for decontaminating the internal space, and a glove 7g for an operator to work is provided on the side surface. In addition, a delivery chamber 14 is provided adjacent to the isolator 7 so as to communicate with the clean room 6, and a glove 14g is also provided in the delivery chamber 14. The gelatin particles processed in the clean room 6 are once accommodated in the delivery chamber 14. The isolator 7 is provided with a plurality of opening and closing doors. A delivery door 7a is provided between the isolator 7 and the delivery chamber 14, and a communication door 7b is provided between the isolator 7 and the vacuum heating means 5. Further, an unloading door 7c is provided for unloading the gelatin particles accommodated in the container after the heat treatment from the isolator 7. The decontamination means 13 fills the internal space with a decontamination medium such as hydrogen peroxide vapor to decontaminate the portions exposed in the internal space, and a conventionally known configuration can be used.

[0017] Hereinafter, a method for producing gelatin particles using the gelatin particle production apparatus 1 having the above configuration will be described with reference to FIGS. 1 and 2. Here, the liquid gelatin as a raw material and the materials necessary for the operation are previously carried into the clean room 6. First, a granulation step of granulating gelatin particles from liquid gelatin is performed. In this embodiment, liquid gelatin having a concentration of 15 wt% is charged into the granulation means 2, the internal temperature of the processing cylinder 2a is set to 90° C., and while spraying the liquid gelatin into the processing cylinder 2a at a rate of 2 g / min, an air flow generating means injects dry air into the processing cylinder 2a at a rate of 70 L / min, and the granulation means 2 is operated for 90 minutes under the above conditions. Then, the liquid droplet-shaped liquid gelatin dries inside the processing cylinder 2a to form seed particles, and as new liquid gelatin colliding with the seed particles dries, the particle size expands, and gelatin particles G are obtained. Here, FIG. 3 shows a graph obtained by analyzing the frequency distribution of the particle size of the gelatin particles G granulated by the granulation means 2 using the laser diffraction / scattering method. The range of the particle size showing the mode value (4 in the figure) is 133.103 μm to 152.453 μm, the frequency is 8.799%, and the cumulative frequency until the particle size is obtained is 63.901%. Thus, when granulating the gelatin particles G using the so-called spray drying method, it can be understood that the particle size exceeds 100 μm, and only a small amount of gelatin particles in the desired range of several tens of μm, for example, 53 μm to 20 μm, can be obtained.

[0018] Next, a first sorting step is performed to sort the gelatin particles G obtained in the granulation step using the first sieve 11a. When the gelatin particles G obtained by the granulating means 2 are put into the first sieve 11a of the first sorting means 11, the first sieve 11a sorts the gelatin particles of 53 μm or less, and the gelatin particles G1 having a particle size exceeding 53 μm remain on the first sieve 11a, and the gelatin particles g of 53 μm or less that have passed through the first sieve 11a are collected in the collection container 11c.

[0019] Next, a pulverizing step is performed to pulverize the gelatin particles G1 remaining on the first sieve 11a in the first sorting step using the pulverizing means 4. That is, in this pulverizing step, the gelatin particles G1 having a particle size exceeding 53 μm are pulverized. In the pulverizing means 4, the hopper 4a supplies the gelatin particles G1 with supply air at 28 m 3 / h, and further, the injection means injects pulverizing air at 48 m 3 / h to pulverize the gelatin particles G1. The processing capacity of the pulverizing means 4 at this time was 1 to 10 g / min.

[0020] Next, a second sorting step is performed to sort the gelatin particles G2 pulverized in the pulverizing step again using the first sieve 11a. The gelatin particles G2 pulverized in the pulverizing step did not pass through the first sieve 11a in the first sorting step, but by being pulverized in the pulverizing step, most of them have a particle size that can pass through the first sieve 11a. Similar to the first sorting step, when the gelatin particles G2 are sorted by the first sieve 11a of the first sorting means 11, a small amount of gelatin particles G3 having a particle size exceeding 53 μm remain on the first sieve 11a, and the gelatin particles g1 of 53 μm or less pass through the first sieve 11a and are collected. Regarding the gelatin particles G3 that did not pass through the first sieve 11a in this second screening step, although they can be discarded, dissolved, and reused, they may be pulverized again to a particle size that can pass through the first sieve 11a, and the second screening step may be performed again.

[0021] Next, a third screening step is performed to screen the gelatin particles g that passed through the first sieve 11a in the first screening step and the gelatin particles g1 that passed through the first sieve 11a in the second screening step by a second sieve 12. In this third screening step, gelatin particles having a particle size of 53 μm or less, which are composed of the gelatin particles g and the gelatin particles g1, are put into the second sieve 12a of the second screening means 12. The second sieve 12a has a smaller mesh size than the first sieve 11a, for example, a mesh size of 20 μm. Therefore, among the gelatin particles g and g1 put into the second sieve 12a, the gelatin particles g2 having a particle size exceeding 20 μm will remain on the second sieve 12a.

[0022] Next, a recovery step is performed to recover the screened gelatin particles g2 obtained in the third screening step as gelatin particles having a desired range of particle sizes. That is, the gelatin particles g2 that did not pass through the second sieve 12a in the second screening means 12 are recovered into a required container, and the gelatin particles g3 that passed through the second sieve 12a are discarded or dissolved and reused because their particle sizes are too small for medical use.

[0023] Next, a heating step is performed to heat-treat the gelatin particles g2 that did not pass through the second sieve 12a in the third screening step and were recovered in the recovery step in a vacuum and non-oxidizing state using a heating means 5. The gelatin particles g2 accommodated in the required container in the recovery step are transferred from the clean room 6 to a delivery room 14 provided adjacent to the isolator 7, and then moved into the internal space of the isolator 7 through the delivery door 7a of the isolator 7. Thereafter, the gelatin particles g2 are accommodated in the heating means 5 through the communication door 7b, and in the heating means 5, heating is performed in an oxidation-free environment at a temperature of 160°C, a heating time of 0.5 to 24 hours, and a pressure of 100 Pa or less. As a result, a crosslinking reaction due to heating occurs in the gelatin particles g2, and they change to a state suitable for medical use, and sterilization by heating is also performed.

[0024] In parallel with the heating step by the heating means 5, the isolator 7 performs a decontamination step of decontaminating the internal space. Before the decontamination step, a container such as a vial for accommodating the gelatin particles g2 is carried in through the carry-out door 7c of the isolator 7 in advance. In this state, with all the opening and closing doors of the isolator 7 closed, the internal space is decontaminated by the decontamination means 13. As a result, the internal space of the isolator 7 and the container are decontaminated.

[0025] Finally, a packaging step is performed in which the gelatin particles g2 that have completed the heating step are accommodated in a container and sealed. When the heating step and the decontamination step are completed, the communication door 7b with the heating means 5 is opened, and the heat-treated gelatin particles g2 are moved to the internal space of the isolator 7. Then, the gelatin particles g2 are manually accommodated in each container by an operator and then sealed. As a result, the gelatin particles g2 are accommodated in all the containers in a sterile state and are taken out to the outside by opening the carry-out door 7c.

[0026] According to the above embodiment, it is possible to efficiently collect the gelatin particles g2 within a desired particle size range from the highly safe gelatin particles G granulated by the granulating means 2. That is, the large gelatin particles G1 that did not pass through the first sieve 11a in the first sorting step are pulverized by the pulverizing means 4, and the pulverized gelatin particles G2 are sorted again in the second sorting step, so that many gelatin particles having a predetermined particle size or less that can pass through the first sieve 11a can be obtained. Thereafter, in the third sorting step, the gelatin particles g and g1 are sorted by the second sieve 12a, so that gelatin particles g2 having a particle size exceeding a predetermined particle size can be obtained, and gelatin particles g2 having a particle size within a desired range can be efficiently obtained. On the other hand, when the granulated gelatin particles are directly pulverized to perform the first sorting step from the above operations, although the particles having a particle size exceeding the desired range are pulverized to an appropriate size, the particles having a particle size within the desired range are pulverized and the particle size becomes smaller, falling below the desired range. Specifically, when gelatin particles g2 were obtained through the first to third sorting steps according to this example, about 26% of the gelatin particles G granulated by the granulating means 2 could be recovered as gelatin particles g2 within the desired particle size range. On the contrary, when the pulverization step was performed without performing the first sorting step, only about 5.6% of the gelatin particles G granulated by the granulating means 2 could be recovered.

[0027] In the above example, the granulating means 2, sorting means 3, and pulverizing means 4 are provided in the clean room 6, but they may be installed in the isolator 7. Also, in the above example, a decontamination step of decontaminating the inside of the isolator 7 is performed during the heat treatment by the heating means 5. However, if the heat-treated gelatin particles g2 can be transferred to the decontaminated sterile isolator 7, it is not necessary to perform the heating step and the decontamination step in parallel. If the gelatin particles g2 are in a state where they are not affected by the decontamination medium, such as being accommodated in the heating means 5, decontamination can also be performed before or after the heat treatment.

Explanation of symbols

[0028] 1 Gelatin particle manufacturing apparatus 2 Granulating means 3 Sorting means 4 Pulverizing means 5 Heating means 6 Clean room 7 Isolator 11 First sieve 12 Second sieve 13 Decontamination means

Claims

1. In a method for producing gelatin particles, which has a granulation step of spraying and drying liquid gelatin to granulate it, and recovering the granulated gelatin particles as gelatin particles within a range having upper and lower limits of several tens of μm as desired, a first screening step of screening the gelatin particles obtained by the granulation step with a first sieve selected in the range of 90 to 45 μm as a first mesh size for screening gelatin particles having a size equal to or less than the upper limit of the desired range; a pulverization step of pulverizing the gelatin particles that have not passed through the first sieve in the first screening step and exceed the upper limit of the desired range; a second screening step of screening the gelatin particles pulverized in the pulverization step with the first sieve; a third screening step of screening the gelatin particles that have passed through the first sieve in the first screening step and the second screening step with a second sieve selected in the range of 40 to 10 μm as a second mesh size for screening gelatin particles having a size equal to or less than the lower limit of the desired range smaller than the first mesh size; a recovery step of recovering the gelatin particles that have not passed through the second sieve in the third screening step and exceed the lower limit of the desired range; and a heating step of heat-treating the recovered gelatin particles. A method for producing gelatin particles, characterized by comprising these steps.

2. The method for producing gelatin particles according to claim 1, wherein in the granulation step, the concentration of the liquid gelatin to be sprayed is 1 to 30 Wt%.

3. The method for producing gelatin particles according to claim 2, wherein in the granulation step, the liquid gelatin having the above concentration is sprayed at 0.5 to 10 g / min, and drying air is injected at 20 to 100 L / min for drying.

4. In a gelatin particle production apparatus comprising granulation means for spraying and drying liquid gelatin to granulate it, and recovering the granulated gelatin particles as gelatin particles within a range having upper and lower limits of several tens of μm as desired, first screening means having a first sieve selected in the range of 90 to 45 μm as a first mesh size for screening gelatin particles having a size equal to or less than the upper limit of the desired range; second screening means having a second sieve selected in the range of 40 to 10 μm as a second mesh size for screening gelatin particles having a size equal to or less than the lower limit of the desired range smaller than the first mesh size; pulverization means for pulverizing gelatin particles; and heating means for heat-treating gelatin particles. The gelatin particles granulated by the granulation means are sorted by the first sorting means, and the gelatin particles that did not pass through the first sieve are ground by the grinding means. Furthermore, the gelatin particles ground by the grinding means are sorted by the first sorting means. The second sorting means sorts the gelatin particles that have been sorted by the first sorting means and passed through the first sieve. A gelatin particle manufacturing apparatus characterized by recovering the gelatin particles that did not pass through the second sieve by the sorting by the second sorting means and performing a heat treatment on the recovered particles by the heating means.

5. The granulation means, the first sorting means, the second sorting means, and the grinding means are provided in a clean space, and the first sorting means and the second sorting means are arranged between the granulation means and the grinding means. The gelatin particle manufacturing apparatus according to claim 4, characterized in that.

6. An isolator whose internal space is maintained in a sterile state is connected to the heating means, and a decontamination means for decontaminating the internal space is provided in the isolator. The gelatin particle manufacturing apparatus according to claim 4 or claim 5, characterized in that the gelatin particles heat-treated by the heating means are carried out into the decontaminated internal space of the isolator.

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