U.S. patent application number 15/668492 was filed with the patent office on 2017-11-16 for vial and method for producing the same.
This patent application is currently assigned to NIPRO CORPORATION. The applicant listed for this patent is NIPRO CORPORATION. Invention is credited to Yoshitaka ISHIMI, Hideo KUWABARA, Shinichiro SENGA, Hideki YAMAUCHI.
Application Number | 20170327405 15/668492 |
Document ID | / |
Family ID | 37431193 |
Filed Date | 2017-11-16 |
United States Patent
Application |
20170327405 |
Kind Code |
A1 |
KUWABARA; Hideo ; et
al. |
November 16, 2017 |
VIAL AND METHOD FOR PRODUCING THE SAME
Abstract
A method for producing a vial with low alkali elution by
removing a deteriorated region caused by processing on an internal
surface of a vial is disclosed. The method involves forming vials
from borosilicate glass tubes including a first step of forming a
borosilicate glass tube into a cup-shaped body by formation of a
bottom of a vial, and a second step of forming the cup-shaped body
into the vial by formation of a mouth of the cup-shaped body.
Inventors: |
KUWABARA; Hideo; (Osaka,
JP) ; YAMAUCHI; Hideki; (Osaka, JP) ; ISHIMI;
Yoshitaka; (Osaka, JP) ; SENGA; Shinichiro;
(Osaka, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NIPRO CORPORATION |
Osaka |
|
JP |
|
|
Assignee: |
NIPRO CORPORATION
Osaka
JP
|
Family ID: |
37431193 |
Appl. No.: |
15/668492 |
Filed: |
August 3, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13846428 |
Mar 18, 2013 |
9751795 |
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15668492 |
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11920425 |
Nov 15, 2007 |
8820119 |
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PCT/JP2006/309674 |
May 15, 2006 |
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13846428 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61J 1/14 20130101; C03C
23/007 20130101; C03B 29/02 20130101; C03B 23/0093 20130101; C03B
23/006 20130101; C03B 23/099 20130101; C03B 23/09 20130101 |
International
Class: |
C03B 23/09 20060101
C03B023/09; C03B 23/00 20060101 C03B023/00; C03C 23/00 20060101
C03C023/00 |
Foreign Application Data
Date |
Code |
Application Number |
May 16, 2005 |
JP |
2005-143307 |
Aug 3, 2005 |
JP |
2005-226042 |
Claims
1. A vial formed from a borosilicate glass tube wherein the vial
has on its internal surface from a bottom toward an opening of the
vial by a certain distance no crater-like pattern.
2. The vial according to claim 1 wherein the crater-like pattern is
visible with a magnification of 1000 times of SEM.
3. The vial according to claim 1 wherein the internal surface has
no crater-like pattern as shown in FIG. 2.
4. The vial according to claim 1 wherein the internal surface is an
intensely heated internal surface which has no crater-like
pattern.
5. The vial according to claim 4 wherein the intensely heated
internal surface is a fire-blasted internal surface which has no
crater-like pattern.
6. The vial according to claim 5 wherein the fire-blasted internal
surface is caused by gas-and-oxygen flames produced by a point
burner.
7. The vial according to claim 5 wherein said fire-blasted internal
surface is caused by fire-blasting the internal surface while
rotating the vial.
8. The vial according to claim 6 wherein said fire-blasted surface
is caused by fire-blasting the internal surface while rotating the
vial.
9. The vial according to claim 5 wherein the internal surface has a
crater-like pattern as shown in FIG. 1 prior to fire-blasting and
has no crater-like pattern as shown in FIG. 2 after
fire-blasting.
10. The vial according to claim 4 wherein the internal surface has
a crater-like pattern as shown in FIG. 1 prior to intensely heating
to have no crater-like pattern as shown in FIG. 2.
Description
[0001] This application is a Divisional of copending application
Ser. No. 13/846,428, filed on Mar. 18, 2013, which was filed as a
Divisional of copending application Ser. No. 11/920,425, filed on
Nov. 15, 2007, which was filed as PCT International Application No.
PCT/JP2006/309674 filed on May 15, 2006, which claims priority
under 35 U.S.C. .sctn.119(a) to Patent Application No. 2005-226042,
filed in Japan on Aug. 3, 2005 and Patent Application No.
2005-143307, filed in Japan on May 16, 2005, all of which are
hereby expressly incorporated by reference into the present
application.
TECHNICAL FIELD
[0002] The present invention relates to a vial with low alkali
elution and a method for producing the same.
BACKGROUND ART
[0003] Automatic vial-forming machines forming vials from
borosilicate glass tubes include a vertical type and a horizontal
type. In both cases, vials are produced by first forming a mouth of
a vial and then forming a bottom of the vial. Chemical quality of
the resultant vials are evaluated by a value of eluted alkali
measured by Method 2 (internal surface method) defined in the
Japanese Pharmacopoeia or a testing method in conformity with the
same. To obtain vials with low alkali elution, it is general
practice to perform a process operated at low temperatures for a
long time, away from use of a process operated at high temperatures
for a short time.
[0004] However, even if the vials are produced by the
low-temperature process, they have a deteriorated region caused by
processing in the form of a belt on the internal surface close to
the bottom of the vial, which has problems such as, for example,
alkali elution affecting pharmaceutical products contained therein.
This deterioration caused by processing is considered to be a
phenomenon such that alkali-containing materials exuded from or
vaporized from the glass are condensed to a plurality of small
droplets and deposited on the internal surface of the vial in the
process of forming the vial bottom from the borosilicate glass
tube.
[0005] In order to lower or prevent elution of alkali from the
condensed droplets on the internal surface of the vial, some
processes have been proposed that include a method (S method) of
allowing the alkali in the deteriorated region to react with
sulphate ions at the final stage of vial forming process, and then
washing the vial with water to remove alkali as sodium sulphate
(Na.sub.2SO.sub.4); and a method of covering the internal surface
of the vial with a thin film of silica (SiO.sub.2) by chemical
vapor deposition (CVD) to prevent elution of alkali. However, the S
method requires an increased cost form washing the vial to remove
white sodium sulphate produced on the internal surface of the vial
and the internal surface after alkali extraction has a markedly
uneven cratered surface. On the other hand, the method of covering
the internal surface of the vial with the silica thin film results
in increased processing cost. [0006] Patent document 1: JP
H06-45481 B [0007] Patent document 2: JP H06-76233B [0008] Patent
document 3: JP 3,268,470
DISCLOSURE OF INVENTION
Problems to be Solved by the Invention
[0009] Accordingly, a first issue to be solved is the deteriorated
region produced by processing on the internal surface of the vial,
and a second issue is the removal of the deteriorated region
produced by processing. It is therefore an object of the present
invention to provide a vial with low alkali elution and a method
for producing the same.
Means for Solving the Problems
[0010] A main feature of the present invention is to minimize the
formation of a deteriorated region produced by processing on an
internal surface of a vial in a process of forming vials from
borosilicate glass tubes by the steps of forming a bottom first and
then forming a mouth. The most distinguishing feature of the
present invention is that the method comprises the steps of forming
a bottom, subsequently removing the produced deteriorated region by
fire blasting with an oxygen-fire flame, and then forming a
mouth.
[0011] According to the present invention, there is provided a
method for producing vials with low alkali elution by forming vials
from borosilicate glass tubes, said method comprising a first step
of forming a borosilicate glass tube into a cup-shaped body to form
a bottom of a vial; and a second step of forming a mouth of said
cup-shaped body to complete a vial with reduced alkali elution.
Also provided is a method for producing vials with low alkali
elution by forming vials from borosilicate glass tubes, said method
comprising a first step of forming a borosilicate glass tube into a
cup-shaped body to form a bottom of a vial; a second step of
fire-blasting an internal surface of said cup-shaped body by a
certain length from the bottom toward an opening of said cup-shaped
body with flames to remove a deteriorated region caused by
processing; and a third step of forming a mouth of said cup-shaped
body to complete a vial with reduced alkali elution. Further
provided is a method for producing vials with low alkali elution by
forming vials from borosilicate glass tubes, said method
comprising: a first step of forming a mouth of a vial; a second
step of forming a bottom of the vial; and a third step of
fire-blasting an internal surface of the vial from the bottom
toward an opening of said cup-shaped body by a certain length with
flames to remove the deteriorated region caused by processing to
complete a vial with reduced alkali elution.
[0012] According to the present invention, there is further
provided a vial produced by forming a borosilicate glass tube,
characterized in that said vial is reduced in alkali elution by a
procedure comprising a first step of forming a borosilicate glass
tube into a cup-shaped body to form a bottom of a vial; and a
second step of forming a mouth of said cup-shaped body.
[0013] Also provided is a vial produced by forming a borosilicate
glass tube, characterized in that said vial is reduced in alkali
elution by a procedure comprising: a first step of forming a
borosilicate glass tube into a cup-shaped body to form a bottom of
a vial; a second step of fire-blasting an internal surface of said
cup-shaped body from the bottom toward the opening of said
cup-shaped body by a certain distance with flames to remove a
deteriorated region caused by forming; and a third step of forming
a mouth of said cup-shaped body to complete a vial with reduced
alkali elution.
[0014] Further provided is a vial produced by forming a
borosilicate glass tube, characterized in that said vial is reduced
in alkali elution by a procedure comprising: a first step of
forming a borosilicate glass tube to form a mouth of a vial; a
second step of forming the resultant glass tube to form a bottom of
the vial; and a third step of fire-blasting an internal surface of
the vial from the bottom toward the opening of said cup-shaped body
by a certain distance with flames to remove a deteriorated region
caused by forming, thereby completing the vial with reduced alkali
elution.
[0015] In addition, the aforesaid flames are gas-and-oxygen flames
produced by a point burner. Further, the aforesaid fire-blasting is
carried out while rotating the vial.
Effects of the Invention
[0016] In the conventional automated forming process of forming
vials from borosilicate glass tubes, the vial is produced by
forming its mouth at the start and then forming its bottom. In the
process of forming the bottom, a number of small droplets
containing alkali (Na.sub.2O) exuded or vaporized from the glass
are deposited on the internal surface of the vial to produce a
deteriorated region caused by processing, which causes alkali
elution.
[0017] In contrast thereto, when the borosilicate glass tube is
formed into a cup-shaped container only by formation of a bottom,
the alkali elution test showed that an amount of alkali eluted from
the cup-shaped container is reduced to one-fifth to one-sixth of
that of the vial formed by the conventional process comprising the
steps of forming a mouth first and forming a bottom. Further, an
internal surface of the above cup-shaped body is subjected to
fire-blasting by means of an oxygen-gas flame from a point burner,
so that the deteriorated region caused by processing can be
completely removed from the container. According to the present
invention therefore it is possible to obtain vials of which a
deteriorated region caused by processing has been minimized or
removed from the deteriorated region caused by processing.
BRIEF DESCRIPTION OF DRAWINGS
[0018] FIG. 1 is an electron microscope photograph of a
deteriorated region affected by processing of a cup C according to
the present invention, and
[0019] FIG. 2 is an electron microscope photograph showing a
deteriorated region affected by processing of a cup C according to
the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0020] The inventors have found that, when the forming steps in the
process of forming borosilicate glass tube into a vial are carried
out in the order of bottom-forming to mouth-forming, the quantity
of eluted alkali is reduced to one-fifth to one-sixth of that of
the vial formed by the conventional process proceeding from
mouth-forming to bottom-forming. In the conventional process
proceeding from mouth forming to bottom forming, alkali-containing
materials exuded from or vaporized from the glass at the time of
bottom forming are trapped in the vial-in-process because of a
narrowed mouth of the vial-in-process, resulting in formation of
the deteriorated region due to processing. In contrast, in the
process proceeding from bottom forming to mouth forming, it is
believed that the vaporized materials are easily released from the
vial-in-process to the outside because of a large opening of the
vial-in-process, resulting in decrease in formation of the
deteriorated region due to processing, which in turn causes
lowering of the alkali elution. When the borosilicate glass is
intensely heated by an oxygen-gas flame of the point burner, the
flame changes from an early blue flame to a yellow flame with
increasing temperature. This results from the flame reaction of
sodium (Na) present in the glass. Based on these observations, the
inventors have found that use of fire-blasting with a sharp and
strong oxygen-gas flame makes it possible to remove the
deteriorated region induced by processing in the internal surface
of the vial. It is believed that the fire-blasting is shot-blasting
with particle ions and molecules in the flame.
[0021] In order to remove the processing-induced deteriorated
region by fire-blasting, it is required to allow the oxygen-gas
flame jet from the point burner to flow out with little resistance
after impingement on the inner surface of the glass tube. To this
end, the vial forming process is required to begin with forming of
a bottom to make a glass tube into a cup-shaped body and then
proceed to forming of a mouth. It should be noted that the quantity
of eluted alkali for evaluation of effects of the forming process
according to the present invention was determined as an amount (mL)
of 0.01 mol/L sulfuric acid consumed in accordance with Method 2
(internal surface method) defined in the Japanese
Pharmacopoeia.
Example 1
[0022] Using the conventional process (mouth-forming to
bottom-forming process), there were produced vials with 60
mm-height.times.12.5 mm-internal mouth diameter (Vial P) from
borosilicate glass tubes with a 30 mm-outer diameter and a 1.5
mm-thickness. The quantity of eluted alkali measured for "vial P"
was 0.74 mL.
[0023] Separate from the above, the same glass tubes were formed
into cup-shaped containers (cup A) by forming a bottom with an
automatic vertical forming machine. The quantity of eluted alkali
measured for "cup A" was 0.10 mL. Using a horizontal forming
machine, "cup A" was provided with a mouth to form it into a vial
(vial Q) in accordance with the forming process of the present
invention (bottom-forming to mouth-forming process). The quantity
of eluted alkali measured for "vial Q" was also 0.10 mL and there
was no change in alkali elution caused by the mouth-forming
process. It is believed that this results from the fact that the
processing temperature of the mouth-forming is lower than that of
the bottom-forming and causes low volatilization of the
alkali-containing material.
TABLE-US-00001 TABLE 1 outer diameter .times. Eluted height .times.
inner diameter alkali Sample thickness (mm) of mouth (mm) (mL) Vial
P 30 .times. 60 .times. 1.5 12.5 0.74 (mouth-forming ->
bottom-forming) Cup A same as above 27.0 0.10 Vial Q same as above
12.5 0.10 (bottom-forming-> mouth-forming)
Example 2
[0024] A borosilicate glass tube with a length of 200 mm was closed
at one end thereof with a silicone rubber stopper, held vertically,
and the filled with a volume of water and autoclaved at 121.degree.
C. for 60 minutes. The quantity of eluted alkali per 100 mL was
0.03 mL. This value was regarded as the quantity of eluted alkali
for the vial never affected by processing.
[0025] Samples (cup B) were formed from the "cup A" in Example 1 by
fire-blasting an internal surface of the "cup A" about 10 mm above
its bottom with an obliquely-directed oxygen-gas flame about 10 cm
long, while holding and rotating the "cup A". The quantity of
eluted alkali measured for "cup B" was 0.03 mL. It is believed that
this results from the fact that the deteriorated region due to
processing is removed by the fire-blasting, thereby recovering the
original surface of the borosilicate glass tubes. The fire-blasting
was done using a point burner with a 1.0 mm bore diameter which is
fed by mixed gas of 0.75 L/min town gas (methane) and 2.20 L/min
oxygen to generate an about 10 cm long flame.
[0026] Then, the "cup B" was provided with a mouth by a horizontal
forming machine to form it into a vial (vial R), of which the
quantity of eluted alkali was 0.03 mL. As mentioned in Example 1,
It is believed that this results from the fact that the processing
temperature of the mouth-forming is lower than that of the
bottom-forming, thus making it harder for the alkali-containing
material to volatilize.
TABLE-US-00002 TABLE 2 outer diameter .times. bore Eluted height
.times. thickness diameter alkali Sample (mm) (mm) (mL)
borosilicate glass 30 .times. 60 .times. 1.5 27.0 0.03 tube Cup A
same as above 27.0 0.10 Cup B same as above 27.0 0.03
(fire-blasting treatment) Vial R same as above 12.5 0.03 (Cup B
-> mouth- forming)
Example 3
[0027] Borosilicate glass tubes with a 40.5 mm-outer diameter and a
1.5 mm-thickness were formed into vials with 78.5
mm-height.times.22.0 mm-internal mouth diameter by the conventional
process (mouth-forming to bottom-forming). The quantity of eluted
alkali measured for the vial was 0.57 mL. Using the automatic
vertical forming machine, a glass tube was provided with a bottom
to prepare a cup-shaped container (cup C). The quantity of eluted
alkali measured for cup C was 0.21 mL. The quantity of eluted
alkali measured for cup D prepared by fire-blasting an internal
surface of the "cup C" was 0.03 mL. The quantity of eluted alkali
measured for a vial made from the cup D by provision of a mouth
with the horizontal forming machine was 0.03 mL.
TABLE-US-00003 TABLE 3 outer diameter .times. bore Eluted height
.times. thickness diameter alkali Sample (mm) (mm) (mL) Vial S 40.5
.times. 78.5 .times. 1.5 22.0 0.57 (mouth-forming->
bottom-forming) Cup C same as above 37.5 0.21 Cup D same as above
37.5 0.03 (fire-blasting treatment) Vial T same as above 22.0 0.03
(Cup D ->mouth- forming)
[0028] Electron microscopic observation on the "cup C" showed that
there is a deteriorated region due to processing, which has a
crater-like pattern resulting from alkali-containing volatiles (a
photograph of FIG. 1). On the other hand, electron microscopic
observation of the cup D, prepared by fire-blasting the
deteriorated region due to processing of "cup C", showed that the
region corresponding to the deteriorated region due to processing
has no crater-like pattern (photograph of FIG. 2). This shows that
the deteriorated region due to processing was removed by
fire-blasting.
Example 4
[0029] Borosilicate glass tubes with a 40.5 mm-outer diameter and a
1.5 mm-thickness were formed into vials with 78.5
mm-height.times.22.0 mm-internal mouth diameter by the conventional
process (mouth-forming to bottom-forming). The quantity of eluted
alkali measured for the resultant vial was 0.57 mL. Using the point
burner which generates a gas-oxygen mixed gas flame (about 10 cm
long), the resultant vials were subjected to fire blasting so that
the flame is blasted to the deteriorated region about 10 mm above
the bottom while rotating the vial. The vial subjected to the
fire-blasting for 40 seconds showed that the quantity of eluted
alkali was reduced to 0.30 mL, while vial subjected to the
fire-blasting for 60 seconds showed that the quantity of eluted
alkali was reduced to 0.13 mL. The vials after the fire-blasting
treatment possess no change in both shape and size. It is to be
noted that the fire-blasting time (seconds) which has an effect on
decrease of alkali elution can be shortened by preheating of the
vials. From these results, it was confirmed that the deteriorated
region of the vials caused by the conventional forming process can
be substantially removed by fire-blasting.
TABLE-US-00004 TABLE 4 Outer diameter .times. bore Eluted height
.times. thickness diameter alkali Sample (mm) (mm) (mL) Vial S 40.5
.times. 78.5 .times. 1.5 22.0 0.57 (mouth-forming->
bottom-forming) Vial T same as above 22.0 0.30 (fire blasting) (40
seconds) Vial U same as above 22.0 0.13 (fire blasting) (60
seconds)
* * * * *