Glass syringe barrels with increased cone breaking forces

Abstract

A glass syringe barrel is provided that has an at least partially conically shaped upper portion and a longitudinal axis. The glass syringe barrel has a top end through which a liquid can be ejected and a bottom end into which a plunger stopper can be pushed. The glass syringe barrel includes, in a direction from the top end to the bottom end, a cone, a shoulder region, and a body region. The shoulder region has and outer contour that has a concave and substantially circular arc-shaped area ci with an outer radius r.sub.1. The outer contour of the glass syringe barrel in the shoulder region is defined by a certain value for r.sub.1.

Claims

1. A glass syringe barrel, comprising: a top end through which a liquid can be ejected; a bottom end into which a plunger stopper can be pushed; a longitudinal axis L.sub.barrel through the top and bottom ends; and a cone region having a first end that corresponds to the top end and a second end, the cone region has a length l.sub.1 and has an outer diameter d.sub.1 at the second end; a shoulder region having a first end that is adjacent to the second end of the cone region and a second end, wherein the shoulder region has an outer contour that comprises a concave and substantially circular arc-shaped area c.sub.1 with an outer radius r.sub.1 beginning below the second end of the cone region and a convex and substantially circular arc-shaped area c.sub.2 with an outer radius r.sub.2 beginning above the second end of the shoulder region; and a body region having a first end that is adjacent to the second end of the shoulder region and a second end that corresponds to the bottom end, wherein the body region has an outer diameter d.sub.2 and a glass thickness n.sub.2, wherein r.sub.1 is in a range from 0.5 to 3 mm, wherein the outer radius r.sub.2 is in a range from 1.2 to 3.1 mm.

2. The glass syringe barrel of claim 1, wherein the outer radius r.sub.1 is in a range from 0.6 to 2.5 mm.

3. The glass syringe barrel of claim 2, wherein the outer radius r.sub.1 is in a range from 0.7 to 2 mm.

4. The glass syringe barrel of claim 1, wherein, if an outer surface of the body region is placed on a plane horizontal substrate, within any given cross-section of the glass syringe barrel that is located in a plane centrically located in the glass syringe barrel and comprising the longitudinal axis L.sub.barrel of the glass syringe barrel, a first function f(x) defines a vertical distance between the substrate and the outer surface at a given position x, k(x)=|f″(x)/[1+f′(x)].sup.3/2| defines an absolute value of the curvature of f(x) at a given position x, and in an interval between x=P.sub.1 and x=P.sub.2 for any concave curvature in the interval a minimum value for (1/k(x))/n.sub.2.sup.2 is at least 0.5 mm.sup.−1, wherein P.sub.1 defines the x-position at which the outer diameter of the glass syringe barrel (100) is 0.95×d.sub.2 and P.sub.2 is P.sub.1+3×n.sub.2.

5. The glass syringe barrel of claim 4, wherein in the interval between x=P.sub.1 and x=P.sub.2 the maximum value of the first derivative f′(x).sub.max of f(x) is less than 18.

6. The glass syringe barrel of claim 1, wherein the outer radius r.sub.2 is in a range from 1.4 to 2.9 mm.

7. The glass syringe barrel of claim 1, further comprising a constriction region that is located between the cone region and the shoulder region, the constriction region having a first end that is adjacent to the second end of the cone region, a second end that is adjacent to the first end of shoulder region and an outer contour c.sub.3, wherein the constriction region has a length l.sub.1′, a minimum outer diameter d.sub.1′<d.sub.1 below the first end of the constriction region and an outer diameter d.sub.1″ at the second end of the constriction region.

8. The glass syringe barrel of claim 7, wherein the outer contour c.sub.3 in the constriction region is conically shaped with d.sub.1′<d.sub.1″ and wherein at the second end of the constriction region, the outer contour c.sub.3 in the constriction region merges into area c.sub.1 without any offset.

9. The glass syringe barrel of claim 8, wherein in the constriction region a first line that runs parallel to the longitudinal axis L.sub.barrel and a second line that runs parallel to the outer contour c.sub.3 and that runs in the same plane as the first line include an angle γ, wherein γ is in the range from 0.3 to 2.5°.

10. The glass syringe barrel of claim 7, wherein the maximum thickness of the glass in the constriction region is in the range from 1.3 to 2.1 mm.

11. The glass syringe barrel of claim 7, wherein the minimum thickness of the glass in the constriction region is in the range from 1.1 to 1.9 mm.

12. The glass syringe barrel of claim 1, wherein the shoulder region comprises an outer shoulder angle α in a range from 6 to 28°.

13. The glass syringe barrel of claim 1, wherein the shoulder region comprises an inner shoulder angle β in a range from 22 to 50°.

14. The glass syringe barrel of claim 1, wherein n.sub.s is the glass thickness in the shoulder region, measured at the point of the inner shoulder surface at which the surface for the first time forms an angle of 30° with longitudinal axis L.sub.barrel, and wherein n.sub.s is in the range from 1.2 to 2 mm.

15. The glass syringe barrel of claim 1, wherein the barrel has a nominal volume V in a range from 0.5 to 11 ml.

16. The glass syringe barrel of claim 1, further comprising a coating that at least partially superimposes the interior surface of the body region.

17. The glass syringe barrel of claim 1, further comprising a needle attached to the cone region via a Luer connector and wherein the needle is sealed with a needle cap.

18. A syringe, comprising: the glass syringe barrel of claim 1; and a plunger stopper in the bottom end.

19. The syringe of claim 18, further comprising a pharmaceutical composition in an inner volume of the glass syringe barrel.

20. A glass syringe barrel, comprising: a top end through which a liquid can be ejected; a bottom end into which a plunger stopper can be pushed; a longitudinal axis L.sub.barrel through the top and bottom ends; and a cone region having a first end that corresponds to the top end and a second end, the cone region has a length l.sub.1 and has an outer diameter d.sub.1 at the second end; a shoulder region having a first end that is adjacent to the second end of the cone region and a second end, wherein the shoulder region has an outer contour that comprises a concave and substantially circular arc-shaped area c.sub.1 with an outer radius r.sub.1 beginning below the second end of the cone region and a convex and substantially circular arc-shaped area c.sub.2 with an outer radius r.sub.2 beginning above the second end of the shoulder region; and a body region having a first end that is adjacent to the second end of the shoulder region and a second end that corresponds to the bottom end, wherein the body region has an outer diameter d.sub.2 and a glass thickness n.sub.2 , wherein r.sub.1 is in a range from 0.5 to 3 mm, wherein n.sub.s is the glass thickness in the shoulder region, measured at the point of the inner shoulder surface at which the surface for the first time forms an angle of 30° with longitudinal axis L.sub.barrel, and wherein n.sub.s is in the range from 1.2 to 2 mm.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Unless otherwise specified in the description or the particular figure:

(2) FIG. 1 shows a cross-sectional view of a syringe comprising a glass syringe barrel 100 according to the present invention into view a plunger stopper 104 has been introduced;

(3) FIG. 2 shows a cross-sectional enlarged view of the top end of a glass syringe barrel 100 according to the present invention that comprises a conically shaped upper portion 101 in the form of a Luer cone;

(4) FIG. 3 shows a cross-sectional enlarged view of the top end 102 of a further glass syringe barrel 100 according to the present invention that comprises a conically shaped upper portion 101 in the form of a Luer cone, wherein the glass syringe barrel further comprises a constriction region 108 that is located between the cone region 105 and the should region 111;

(5) FIG. 4 shows the determination of angle γ in the constriction region 108;

(6) FIG. 5A shows a cross-sectional enlarged view of the top end 102 of the glass syringe barrel 100 shown in FIG. 3, wherein in contrast to FIG. 3 the glass syringe barrel 100 with the outer surface of the body region 114 is laying on a substrate 119;

(7) FIG. 5B shows function f(x) by means of which the curvature k(x) of the outer contour of the glass syringe barrel in the shoulder region 111 can be determined;

(8) FIG. 6A shows in a side view the localization of plane 120 that is used to determine the local curvature of function f(x) within the range from P.sub.1 to P.sub.2;

(9) FIG. 6B shows in a top view the localization of plane 120 that is used to determine the local curvature of function f(x) within the range from P.sub.1 to P.sub.2;

(10) FIG. 7 shows the determination of r.sub.1;

(11) FIG. 8 shows the determination of n.sub.s;

(12) FIG. 9 shows the determination of β;

(13) FIG. 10 shows a glass syringe barrel 100 according to the present invention with a tip cap 117 attached to the conically shaped upper portion 101;

(14) FIGS. 11A-F illustrate steps I), II) and III) of process 1 according to the invention for the preparation of a glass syringe barrel 100;

(15) FIG. 12 illustrates the mechanical load that is applied onto the cone of the glass syringe barrels when calculating the maximum tensile stresses in Comparative Example 2 and Example 2;

(16) FIGS. 13A-B illustrate the results of the calculations in Comparative Example 2 and Example 2.

DETAILED DESCRIPTION

(17) FIG. 1 shows a cross-sectional view of a syringe comprising a glass syringe barrel 100 according to the present invention having the length l.sub.3 and an outer diameter d.sub.2 in the body region 114 into view a plunger stopper 104 has been introduced. As can be seen in FIG. 1, the syringe barrel 100 comprises a top end 102 with a conically shaper upper portion 102 and a bottom end 103 into which the plunger stopper 104 has been introduced.

(18) FIG. 2 shows a cross-sectional enlarged view of the top end 102 of the glass syringe barrel 100 shown in FIG. 1 that comprises the conically shaped upper portion 101 (the section of the glass syringe barrel 100 that is shown in FIG. 2 corresponds to the area that is encompassed by the dotted circle in FIG. 1). As can be seen in FIG. 2, the conically shaped upper portion 101 of the glass syringe barrel 100 is in the form of a Luer-slip style connector and comprises in the embodiment shown in FIG. 2 a cone region 105 having a first end 106 that corresponds to the top end 102 of the glass syringe barrel 100 and a second end 107, wherein the cone region 105 has a length l.sub.1 and an outer diameter d.sub.1 at the second end 107. Adjacent to the cone region 105 is a shoulder region 111 having a first end 112 that is adjacent to the second end 107 of the cone region 105 and a second end 113, wherein the outer contour of the shoulder region 111 comprises a concave and substantially circular arc-shaped area c.sub.2 (see the dashed and bold marked line in the upper part of the right side of the shoulder region) with an outer radius r.sub.1 beginning below the second end 110 of the constriction region 108 and a convex and substantially circular arc-shaped area c.sub.3 (see the continuous and bold marked line in the upper part of the right side of the shoulder region) with an outer radius r.sub.2 beginning above the second end 113. As also shown in FIG. 2 the shoulder region 111 is characterized by an outer shoulder angle α and an inner shoulder angle β. Adjacent to the should region 111 is a body region 114 (see also FIG. 1) into which the syringe plunger 104 can be pushed, having a first end 115 that is adjacent to the second end 113 of the shoulder region 111 and a second end 116 that corresponds to the bottom end 103 of the glass syringe barrel 100, wherein the thickness of the glass in the body region 114 is n.sub.2. The diameter d.sub.2 of the body region 114 corresponds to the diameter of the glass tube 126 hat us used to manufacture the glass syringe barrel 100 according to the present invention (see FIGS. 11A-11F).

(19) FIG. 3 shows a cross-sectional enlarged view of the top end 102 of a further glass syringe barrel 100 according to the present invention that comprises a conically shaped upper portion 101 in the form of a Luer cone, wherein the glass syringe barrel further comprises a constriction region 108 that is located between the cone region 105 and the should region 111. The constriction region 108 comprises a first end 109 that is adjacent to the second end 107 of the cone region 105, a second end 110 that is adjacent to the first end 112 of shoulder region 111 and an outer contour c.sub.3, wherein the constriction region 108 has a length l.sub.1′, a minimum outer diameter d.sub.1: <d.sub.1 below the first end 109 of the constriction region 108 and an outer diameter d.sub.1″ at the second end 110 of the constriction region 108. In this context it is furthermore preferred that the outer contour c.sub.3 of the glass syringe barrel in the constriction region is conically shaped with d.sub.1′<d.sub.1″ and wherein at the second end of the constriction region c.sub.3 merges into c.sub.1 without any offset. It is also preferred that in the constriction region 108 a first line 117 that runs parallel to the longitudinal axis L.sub.barrel and a second line 118 that runs parallel to c.sub.3 and that runs in the same plane as the first line 117 include an angle γ, wherein γ is in the range from 1 to 3°. FIG. 4 shows how to determine the angle γ in the constriction region 108, this angle defining the extend of the conical shape of the constriction region.

(20) The glass syringe barrel 100 according to the present invention is characterized by a well-defined outer contour in the transition region between the shoulder region 111 and, if present, of the constriction region 108 as well. If the glass syringe barrel 100 is placed on a plane horizontal substrate 119 with the outer surface of the body region 114 on it as shown in FIG. 5A, function f(x) defines the vertical distance between the substrate 119 and the outer surface of the glass syringe barrel 100 at a given position x and thus the outer contour of the glass syringe barrel 100 in that area (see FIG. 5B). From that function the curvature k(x) at a given position x of the outer contour can be calculated as
k(x)=|f″(x)/[1+f′(x).sup.2].sup.3/2).

(21) The glass syringe barrel according to the present invention is now characterized in that interval between x=P.sub.1 and x=P.sub.2 for any concave curvature in this interval the minimum value for (1/k(x))/n.sub.2.sup.2 is at least 0.5 mm.sup.1, wherein P.sub.1 defines the x-position at which the outer diameter of the glass syringe barrel 100 is 0.95×d.sub.2 and P.sub.2 is P.sub.1+3×n.sub.2 (see FIG. 5A).

(22) FIGS. 6A and 6B show in a side view and in a top view the localization of plane 120 in the glass syringe barrel 100 that is used to determine the local curvature of function f(x) within the range from P.sub.1 to P.sub.2 by means of the approach that is shown in FIGS. 5A and 5B. Plane 120 corresponds to the plane that is centrically located in the glass syringe barrel 100 and that comprises the longitudinal axis L.sub.barrel of the glass syringe barrel 100.

(23) FIG. 7 shows how to determine the outer radius r.sub.1 of the concave and substantially circular arc-shaped area c.sub.1 of the shoulder region 111. r.sub.1 can be determined geometrically in cross-sectional images of the glass syringe barrel 100 by applying a bevel circle to the first inflection point IP (i. e. the first one that appears when entering the outer contour of the shoulder region 111 from the top end 102 of the glass syringe barrel 100) of function f(x) (i. e. the first point at which the condition f″(x)=0 is fulfilled) and to a straight line 121 extending the outer contour of the cone region 105. r.sub.2 can be determined geometrically by applying a circle adjacent to a straight line 122 extending the outer contour of the body region 114 and by increasing the diameter of the circle until a maximum overlap between the outer contour of the shoulder region 111 and a segment of the arc is reached. The radius of the thus obtained circle is r.sub.2.

(24) FIG. 8 shows how to determine the thickness n.sub.s of the glass in the shoulder region 111. n.sub.s is measured at that point P.sub.3 of shoulder region at which a tangent at the outer surface for the first time forms an angle of 30° to the syringe axis L.sub.barrel as this is shown in FIG. 8. n.sub.s is determined in a direction perpendicular to that line. For that purpose, a line is drawn perpendicular to that tangent in P.sub.3. The point at which this perpendicular line crosses the inner surface is named P.sub.4. A third line is drawn that runs parallel to tangent and that goes through P.sub.4. n.sub.s corresponds to the distance between these two parallel lines.

(25) FIG. 9 shows how to determine the inner shoulder angle β. β is measured at that point of the inner shoulder whose distance to the syringe axis L.sub.barrel is [d.sub.c,inner+d.sub.2,inner)/4. d.sub.c,inner corresponds to the inner diameter of the channel 125 at the top end 102 of the glass syringe barrel 100 and &inner corresponds to the inner diameter of the body region 114.

(26) FIG. 10 shows a glass syringe barrel 100 according to the present invention with a tip cap 126 attached to the conically shaped upper portion 101.

(27) FIGS. 11A-F illustrate steps I), II) and III) of process 1 according to the invention for the preparation of a glass syringe barrel 100 according to the present invention. In process step I) a glass tube 127 having a longitudinal axis L.sub.tube, a first end 129 and a further end 128 is loaded into a machine, preferably a rotary machine, the glass tube 127 having a wall thickness nz and an outer diameter dz. In process step II) the glass tube 127, while rotating around its longitudinal axis, is heated to a temperature above its glass transition temperature, preferably above its softening temperature, with a heating element 130 (indicated by the candle flames shown on the left in FIG. 11A), preferably with a flame 130. In process step III), while the glass tube 127 is still rotating around its longitudinal axis, the first end 129 that has been heated is shaped by using molding tools 131 that act on predetermined positions of the outer surface of the glass tube 127 at the first end 129 to form a conically shaped upper portion 101 as shown in FIGS. 11B and 11E. In the process shown in FIGS. 11A-11F the conically shaped upper portion 101 is formed in two steps: in a first step using a first set of molding tools 131 a Luer end precursor 132 is formed that does not have the final shape of the conically shaped upper portion 101 according to the present invention (see FIGS. 11B and 11C). The Luer cone precursor 132 is then again heated as shown in FIG. 11D and is then finally shaped using a second set of molding tools 133 as shown in FIG. 11E to obtain a glass tube 127 with finished conically shaped upper portion 101 (see FIG. 11E). The shape of the molding tools 131,133 that are used in this shaping process as well as the extent to which they are pressed against the molten region of the glass tube 127 have to be adopted to ensure that the desired geometry particularly in the transition state between the shoulder region 111 and the cone region 105 (or, if present, the constriction region 108) is obtained.

(28) In a further process step V) the glass tube with finished conically shaped upper portion 101, while rotating around its longitudinal axis, is cut at a predetermined position above the first end 129 to obtain a glass tube with a length l.sub.tube comprising a first end 128 that has been shaped by means of process steps I) to III) and second end. In a further process step VI) the second end of the glass tube, while rotating around its longitudinal axis, is heated to a temperature above its glass transition temperature, preferably above its softening temperature, with a heating element, preferably with a flame. In a further process step VII), while the glass tube is rotating around its longitudinal axis, the second end that has been heated using is shaped using one or more molding tools that act on predetermined positions of the outer surface of the glass tube at the first end to, for example, form a finger flange (process steps V) to VII) are not shown in FIGS. 11A-11F).

LIST OF REFERENCE NUMERALS

(29) 100 glass syringe barrel according to the invention 101 conically shaped upper portion 102 top end 103 bottom end 104 plunger stopper 105 cone region 106 first end of the cone region 105 (=top end 102) 107 second end of the cone region 105 (=first end 112 of the shoulder region 111 or first end 109 of the constriction region 108) 111 shoulder region 112 first end of the shoulder region 111 (=second end 107 of the cone region 105 or second end 110 of the constriction region 108) 113 second end of the shoulder region 111 (=first end 115 of the body region 114) 114 body region 115 first end of the body region 114 (=second end 113 of the shoulder region 111) 116 second end of the body region 114 (=bottom end 103) 108 constriction region 109 first end of the constriction region 108 (=the second end 107 of the cone region 105) 110 second end of the constriction region 108 (=first end 112 of the should region 111) 117 first line 118 second line 119 plane and horizontal substrate 120 cross-sectional plane in the middle of the glass syringe barrel 100 121 elongation of the outer contour of the cone region 105 122 elongation of the outer contour of the body region 114 123 tangent at the outer surface of the shoulder region 111 that includes an angle of 30° with l.sub.barrel 124 tangent at the inner surface of the shoulder region 111 that includes an angle of 30° with l.sub.barrel 125 channel at the top end 102 126 tip cap 127 glass tube 128 further end of the glass tube 129 first end of the glass tube 130 heating element 131 first set of forming tools 132 Luer end precursor 133 second set of molding tools 134 glass tube with finished Luer end