U.S. patent application number 09/564758 was filed with the patent office on 2003-07-17 for glass container for medicinal purposes.
Invention is credited to Auchter-Krummel, Petra, Geiger, Andreas, Spallek, Michael, Walther, Marten.
Application Number | 20030134060 09/564758 |
Document ID | / |
Family ID | 7907452 |
Filed Date | 2003-07-17 |
United States Patent
Application |
20030134060 |
Kind Code |
A1 |
Walther, Marten ; et
al. |
July 17, 2003 |
GLASS CONTAINER FOR MEDICINAL PURPOSES
Abstract
The glass container stores and preserves pharmaceutical or
diagnostic solutions for medicinal purposes. In order to provide a
silicone-free but residue free bottle after emptying, the glass
container is provided with an amorphous transparent and
pharmaceutically acceptable anti-adherent coating (4) over the
entire interior surface of the glass container from its bottom over
the wall (3) to the closure device (2). This anti-adherent coating
(4) has a contact angle for wetting with water of
.gtoreq.80.degree., even after autoclaving at about 120.degree. C.
for about 20 min, contains silicon, oxygen, carbon and hydrogen and
is deposited according to a PECVD method, especially a PICVD
method.
Inventors: |
Walther, Marten;
(Engelstadt, DE) ; Geiger, Andreas; (Kirchlengern,
DE) ; Auchter-Krummel, Petra; (Vendersheim, DE)
; Spallek, Michael; (Stauferring 25, DE) |
Correspondence
Address: |
Striker Striker & Stenby
103 East Neck Road
Huntington
NY
11743
US
|
Family ID: |
7907452 |
Appl. No.: |
09/564758 |
Filed: |
May 4, 2000 |
Current U.S.
Class: |
428/34.6 |
Current CPC
Class: |
C03C 17/22 20130101;
C03C 17/30 20130101; Y10S 215/03 20130101; C23C 16/045 20130101;
Y10T 428/1317 20150115; C03C 2217/282 20130101; Y10T 428/1321
20150115; C03C 2218/153 20130101 |
Class at
Publication: |
428/34.6 |
International
Class: |
B32B 001/02 |
Foreign Application Data
Date |
Code |
Application Number |
May 7, 1999 |
DE |
199 21 303.8-45 |
Claims
We claim:
1. A glass container for storing and preserving pharmaceutical or
diagnostic solutions for medicinal purposes, wherein said glass
container comprises a closure device (2) and an amorphous,
transparent and pharmaceutically acceptable anti-adherent coating
(4) provided on an entire interior surface thereof over the entire
interior surface up to the closure device, and wherein the
anti-adherent coating has a contact angle for wetting by water of
.gtoreq.80.degree., even after autoclaving at about 120.degree. C.
for about 20 min, and the anti-adherent coating contains silicon,
oxygen, carbon and hydrogen and is deposited ny means of a
plasma-enhanced chemical vapor deposition process.
2. The glass container as defined in claim 1, wherein said
plasma-enhanced chemical vapor deposition process is a
plasma-pulsed chemical vapor deposition process.
3. The glass container as defined in claim 1, wherein said
anti-adherent coating (4) contains at least 1% by weight of said
silicon.
4. The glass container as defined in claim 1, wherein said
anti-adherent coating (4) contains at least 5% by weight of said
carbon.
5. The glass container as defined in claim 1, wherein said coating
(4) contains fluorine.
6. The glass container as defined in claim 5, wherein, according to
the following reciprocal relationship, when the coating contains
less than 0.1% by weight fluorine, then the coating contains
greater than or equal to 10% by weight of said carbon, but when the
coating contains greater than or equal to 0.1% by weight fluorine,
then the coating contains greater than or equal to 5% by weight
carbon.
7. The glass container as defined in claim 1, wherein said
anti-adherent coating is free of silicones.
8. The glass container as defined in claim 1, wherein said
anti-adherent coating is free of polydimethylsiloxanes.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a glass container for
medicinal purposes, and, more particularly, to a glass container
for storing and preserving pharmaceutical or diagnostic solutions
for medicinal purposes, which is provided with an anti-adherent
coating on its interior surface or surfaces.
[0003] 2. Prior Art
[0004] Glass containers for medicinal purposes, i.e. containers
having pharmaceuticals or diagnostics as contents, are on the
market in a most wide variety of embodiments, in order to take into
account their respective purposes, associated administration forms
and the respective contents.
[0005] Glass containers for medicinal contents should have interior
surfaces which have the least possible adherence for their
contents, i.e. as large as possible a wetting angle for aqueous
contents, in order to permit a complete emptying of residues from
the container. This is particularly true for comparatively small
glass containers with very expensive contents.
[0006] Glass containers for medicinal purposes have been treated
with silicone oils (polydimethylsiloxane oil) or silicone oil
emulsions, in order to produce anti-adherent interior surfaces.
This has been disclosed in U.S. Pat. No. 2,504,482, among other
prior art references. This method is also described in European
medical formularies.
[0007] The main disadvantage of this method is that silicone oil is
dispensed from the surfaces and that the silicone oil may be
introduced into human or animal bodies. Furthermore undesirable
adsorption phenomenon occur on the silicone-coated surface, which
are remarkable, especially protein-binding. Furthermore heavy metal
impurities are unavoidably present in the silicone oil. Thus
suitable expensive testing is prescribed in European formularies.
Furthermore auxiliary substances (e.g. detergents), which must be
used for stabilizing silicone emulsions, are critical.
[0008] Methods for modification of the interior surfaces of the
glass container using silanes, silazanes, etc, are known (GB
2,230,260 A) as well as by application of silicone oil. A monolayer
is deposited on the surfaces from the liquid or gas phase after an
expensive cleaning process, which often uses reactive acids, such
as chromo-sulfuric acid, etc.
[0009] This process has the disadvantage that a fresh expensive
washing process is required after the surface treatment, in order
to remove the residual chemicals most completely. Furthermore no
silane or silanized layers, which resist the action of the typical
pharmaceutical tests sufficiently, which especially withstand
autoclaving at 121.degree. C. for 20 minutes, are currently
known.
SUMMARY OF THE INVENTION
[0010] It is an object of the present invention to provide a glass
container for medicinal purpose of the above-described kind, so
that its interior surface has an outstanding anti-adherent
property, it is equal to the typical pharmaceutical stress test
conditions and it introduces no silicone into the solution found in
the glass container.
[0011] According to the invention this object is attained with a
glass container for storing and preserving pharmaceutical or
diagnostic solutions for medicinal purposes, comprising a container
closure device and an amorphous, transparent and pharmaceutically
acceptable anti-adherent coating provided on the entire interior
surface of the glass container over the entire interior surface up
to the closure device, and wherein the anti-adherent coating has a
contact angle for wetting with water of .gtoreq.80.degree., even
after autoclaving at about 120.degree. C. for about 20 min,
contains the elements Si, O, C and H and is deposited by means of a
plasma-enhanced chemical vapor deposition method (PECVD),
preferably by means of a plasma-pulsed chemical vapor deposition
method (PICVD).
[0012] Medicinal glass containers of this type, i.e. according to
the invention, have interior surfaces that to a large extent reject
water or wetting with water, which permits a nearly complete
emptying of the container. It also has the great medically related
advantage that no silicone substances are introduced into the
pharmaceutical or diagnostic contents and thus into the human
body.
[0013] Tests have shown that the anti-adherent layer or coating
according to the invention is equal to typical pharmaceutical
stress test conditions, e.g. typical sterilization conditions,
without loosing its function. The glass container according to the
invention is thus to a large extent pharmaceutically
acceptable.
[0014] Preferably the anti-adherent layer comprises at least 1% by
weight silicon and at least 5% by weight carbon. The hydrophobic
properties of the coating can be augmented, when the anti-adherent
coating contains fluorine according to a further embodiment of the
invention.
[0015] According to a preferred embodiment of the invention the
percentage content of fluorine in the anti-adherent layer is
related to the percentage content of carbon by the following
reciprocal relationship:
[0016] When fluorine <0.1% by weight, then C.gtoreq.10% by
weight;
[0017] When F.gtoreq.0.1% by weight, then C.gtoreq.5% by
weight.
BRIEF DESCRIPTION OF THE DRAWING
[0018] The objects, features and advantages of the invention will
now be illustrated in more detail with the aid of the following
description of the preferred embodiment, with reference to the
accompanying sole FIGURE which is a partially side, partially
cutaway cross-sectional view through a glass container for
medicinal purposes according to the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0019] The sole FIGURE shows a glass container 1 for medicinal
purposes in a configuration suitable for a typical application,
which is provided with a conventional closure device 2. The glass
container 1 serves for storage and preservation of a pharmaceutical
or diagnostic solution 5.
[0020] The glass container 1 is preferably made from a glass type I
according to German Dispensatory, 10th Edition, corresponding to a
borosilicate glass. The particular glass type mentioned above and
the shape of the glass bottle are features of preferred
embodiments. According to the invention the glass bottle may also
have other shapes and can be made from other types of glass, which
have the required properties for other applications. Especially the
glass bottle may be made from glass of a lower hydrolytic class,
especially the so-called neutral glass.
[0021] It is desirable that the interior of the glass bottle should
reject water to a large extent. That means that it should have as
large as possible a wetting angle for its aqueous contents 5,
especially in order to permit complete emptying so as to minimize
any residue left in the bottle. This is also true for a
comparatively small glass container with very expensive
contents.
[0022] In order to achieve this behavior, a special coating 4 is
provided over the whole interior surface of the wall 3 of the glass
bottle 1. This coating comprises an anti-adherent layer with a
contact angle for water of .gtoreq.80.degree., which is
pharmaceutically acceptable, i.e. free of heavy metals and stable
under the usual test conditions, especially autoclaving for 20
minutes at 121.degree. C. and/or in hot air sterilization for 30
minutes at 300.degree. C. The layer is amorphous, clear and
transparent and contains the elements Si, O, C and H, with silicon
content of at least 1% by weight and a C content of at least 5% by
weight. Preferably the layer 4 also contains fluorine, whose
content is in a reciprocal relationship to the carbon content. In
other words,
[0023] when fluorine <0.1% by weight, then C.gtoreq.10% by
weight;
[0024] when F.gtoreq.0.1% by weight, then C.gtoreq.5% by
weight.
[0025] The coating or layer 4 is produced by means of a
plasma-enhanced chemical vapor deposition process (PECVD). In this
process a plasma-assisted layer deposition from the gas phase
occurs, in which the layer material is supplied in the form of
so-called precursor gases. These pre-cursor gases are broken down
with the required energy being supplied to the system by electrical
high frequency plasma, particularly in a plasma-pulsed chemical
vapor deposition process (PICVD).
[0026] These processes and their associated apparatus are well
known. Examples are described in DE 196 29 877 C1 and DE 44 38 359
A1, which were produced by the present applicant.
[0027] The container for medical purposes according to the present
invention has the following properties:
[0028] a) its interior surface rejects water, so that its aqueous
contents have the greatest possible wetting angle with its interior
surface, in order to obtain complete emptying without leaving any
residue;
[0029] b) its interior surface does not bind proteins;
[0030] c) its interior surface is free of silicone
(polydimethylsiloxanes)- ;
[0031] d) it is stable during typical pharmaceutical stress test
conditions and/or terminal sterilization (autoclaving in steam at
121.degree. C. for 20 minutes);
[0032] e) it has a high degree of transparency;
[0033] f) it has a high stability against washing processes, drying
processes, hot air sterilization, filling processes and closing
processes, including a washing process with hot distilled water and
a hot air sterilization with temperatures up to 300.degree. C. and
dwell times of up to 30 minutes;
[0034] g) it provides a high degree of chemical purity, i.e. it is
not necessary to use solvents and/or aggressive chemicals for
surface activation or cleaning; and it may be produced by a simple
method.
[0035] It has been surprisingly found that not only the adherence
of particles in aqueous suspensions on container interior surfaces
is drastically reduced, but also that this is also true for
suspensions, which contain an inert propellant gas, such as e.g.
R134a, R127. This is also true for alcoholic suspensions.
EXAMPLES
[0036] The following two examples which are representative of
numerous other tests are described in the following paragraphs.
These examples show that the glass container according to the
invention has properties that are superior to those of the prior
art.
Example 1
Coating According to a PECVD Method
[0037] Glass containers in the form of glass bottles are placed in
a PECVD reactor, whose structure corresponds principally to that
disclosed in DE 44 38 359 A1. A gas nozzle device extends into the
mouth of the bottle. The reactor is evacuated to 0.05 mbar by a
pump. Then a mixture of HMDSO (5 sccm) and
C.sub.6F.sub.10(CF.sub.3).sub.2 is conducted into the bottle
through the gas nozzle device. RF power is coupled to an electrode
in the reactor inductively by means of coils through a matching
network and ignites a plasma in the reactor. The entire apparatus
is arranged within an electrical shielding. In this process the
reaction gas is converted into a coating in the whole bottle at
about 300 W HF power (13.56 MHz).
[0038] A contact angle of 95.degree. to 102.degree. (relative to
water) is produced in all bottles by this process. This contact
angle becomes 85.degree. to 95.degree. during autoclaving at
121.degree. C. for 20 minutes. All bottles were filled with an
aqueous suspension. After a storage time of 1 week the pouring
behavior was tested. In contrast to the uncoated bottles, in which
a residue of flecks of the suspension remained over the entire
interior surface after emptying the bottles, the bottles coated in
the above-described manner according to the invention, could be
completely emptied without leaving a residue.
Example 2
Coating According to a PICVD Method
[0039] Glass containers in the form of glass bottles are placed in
a PICVD reactor, whose structure corresponds principally to that
disclosed in DE 196 29 877 C1. The reactor is evacuated to 0.9 mbar
by a pump. In these bottles a gas mixture comprising 10 sccm HMDSO,
5 sccm O.sub.2 and 2 sccm C.sub.6F.sub.6 is supplied by a supply
device. Pulsed power was provided at 2.45 GHz by a microwave
discharge source, which ignites a plasma in the glass bottle. After
deposition of a 30 nm layer the microwave power is turned off and
the bottles are aerated. The tests found that after the coating is
formed the contact angle for water was 91.degree. to 105.degree..
This contact angle is reduced about 6.degree. on average after
autoclaving. This behavior of a watery suspension that is poured
out of bottles coated in this manner is similar to that described
in connection with the previous PECVD method.
[0040] The disclosure in German Patent Application 199 21 303.8 of
May 7, 1999 is incorporated here by reference. This German Patent
Application describes the invention described hereinabove and
claimed in the claims appended hereinbelow and provides the basis
for a claim of priority for the instant invention under 35 U.S.C.
119.
[0041] While the invention has been illustrated and described as
embodied in a glass container for medicinal purposes, it is not
intended to be limited to the details shown, since various
modifications and changes may be made without departing in any way
from the spirit of the present invention.
[0042] Without further analysis, the foregoing will so fully reveal
the gist of the present invention that others can, by applying
current knowledge, readily adapt it for various applications
without omitting features that, from the standpoint of prior art,
fairly constitute essential characteristics of the generic or
specific aspects of this invention.
[0043] What is claimed is new and is set forth in the following
appended claims.
* * * * *