United States Patent [191 Hurschman et al.
[54] HYPODERMIC DEVICES [75] Inventors: Alfred A. Hurschman, Streetsboro; Thomas P. Schiller, Pepper Pike, both of Ohio [73] Assignee: Ampoules Inc., Macedonia, Ohio [22] Filed: Feb. 11, 1971 [21] Appl. No.: 114,493
[52] US. Cl. ..128/218 M, 128/218 DA, 128/216, 128/218 D, 128/272 [51] Int. Cl. ..A61m 5/00, A61j 1/00 [58] Field ofSearch ..128/215,2l6,218 R, 128/218 D,218 DA,218 N,218 1 ,220,272
[56] References Cited UNITED STATES PATENTS 2,159,217 5/1939 Lozier et al ..128/218 D 2,193,322 3/1940 Lozier et a1 ..128/218 M 2,567,001 9/1951 Watson ..l28/2l8 D 2,665,687 1/1954 Brown 128/218 D 2,696,212 12/1954 Dunmire ..l28/216 2,704,072 3/1955 Sarnoff 128/218 D 2,888,924 6/1959 Dunmire 128/218 D 3,236,237 2/1966 Dunmire ..l28/2l6 3,477,432 11/1969 Shaw; ..128/218 M 3,066,671 12/1962 Cohen ..l28/272 FOREIGN PATENTS OR APPLICATIONS 1,491,699 10/1969 Germany ..l28/220 863,907 3/1961 Great Britain ..l28/173 H Primary Examiner-Richard A. Gaudet Assistant Examiner-J. C. McGowan Attorney-McNenny, Farrington, Pearne & Gordon [5 7] ABSTRACT Hypodermic ampoules of the contained-needle type, a method of assembling and filing such ampoules, and combinations of such ampoules with so-called applicators for actuating the ampoules to make injections are disclosed. Each of several ampoule forms has a plurality of cylindrical, medicament-containing chambers and a plunger closing one end of one of the chambers. A hollow needle is fixed to the plunger and is initially contained within such a chamber. The other end of the ampoule is sealed by a diaphragm which is pressed against a beaded end portion of a cylinder and is sealed thereto by a cup-shaped clip which snaps over the beaded end portion to thereby compress the diaphragm against the end portion. The clip has a peripheral rim about a recessed bottom end which stretches the patients skin to facilitate the injection. According to the invention, the ampoule includes multiple chambers for premixing a medicament with at least one other medicament and dispensing the mixture by, for example, injecting it either subcutaneously or intramuscularly.
5 Claims, 14 Drawing Figures PATENTEU W29 I975 3, 735,761
SHEET 1' BF 3 ATTOFA/YS 1 HYPODERMIC DEVICES BACKGROUND OF THE INVENTION This invention relates to disposable hypodermic ampoules that provide a chamber containing both a medicament to be injected and the hypodermic needle through which the injection is made, the injection being performed by collapsing or otherwise actuating the device to project the pointed end of the needle through a puncturable wall of the ampoule and then into the patient while reducing the volume of the medicamentcontaining chamber to express the medicament through the needle and into the patient. Such ampoules are referred to herein by the generic designation, contained-needle type.
A number of drug compounds, including some antibiotics, some vaccines, and several other injectable products, require that an active ingredient (usually in a powder form) be mixed with an injection vehicle (usually water) shortly before administration. One widely accepted procedure for mixing powder and liquid medicament components is to provide them in separate vials, each having its own rubber stopper closing its outlet opening. The liquid is withdrawn from its vial by a needle and syringe and is then injected into the vial containing the powder. The thus mixed liquid and powder in the latter vial, after shaking it where required, are withdrawn as a dispersion by the same needle and syringe, and the injection is effected therewith in a conventional manner.
Attempts have been made to provide a multicompartment vial wherein liquid and solid components to be mixed prior to injection are separately contained in a manner that permits mixing them within the common vial. For example, U.S. Pat. No. 2,495,942 to W. A. Nosek provides an outer container having an inner con- I tainer mounted therein. The outer container contains ent invention relates, apart from other objections thereto.
Another proposal for providing a multichamber container is set forth in U.S. Pat. No. 3,342,180 to Sandhage et al., dated Sept. 19, 1967. In that patent, the patentees provide a vial which is separated into two chambers by a plunger. Power is provided in a lower chamber and liquid is provided in the upper chamber. The plunger is provided with a one-way check valve so that, upon retraction of the plunger, the liquid is forced through the valve and into the compartment containing the powder. The vial is provided with an external needle at its lower end so that the mixed medicament may be injected into the patient. Again, apart from other objections thereto, such an arrangement is not readily applicable to the contained-needle type of hypodermic ampoules to which the present invention relates.
As a result of the foregoing problems, and numerous others, prior hypodermic ampoules of the containedneedle type, to which the present invention relates, have all been subject to severe limitations on their practical utility, and their uses have been restricted accordingly. The present invention is directed to the provision of a basic ampoule design of the containedneedle type that is adaptable for making both subcutaneous and intramuscular injections of two or more separated medicament components that are mixed in the ampoule itself. A major objective is to achieve all of this 1. with a maximum utilization of basic parts of both the ampoules and applicators therefor, 2. with a minimum variation in the techniques of assembling, filling, and using the ampoules, and 3. while overcoming or avoiding the many problems that have heretofore prevented general use of the desirable, contained-needle type of injection device.
SUMMARY OF THE INVENTION This invention provides a multichamber, hypodermic device which includes first and second coaxially disposed cylinders. The cylinders respectively provide first and second, medicament-containing chambers, the adjacent ends of which are separated by a first, puncturable, piston-like diaphragm. This first diaphragm extends across and around the end of the first cylinder to close and seal the same and is slidably mounted in the adjacent end of the second cylinder to close and separately seal the same. These two seals are exposed to and separated by the ambient atmosphere so as to avoid liquid seepage from one chamber into the other. The other end of the first cylinder slidably carries a plunger. A hypodermic needle is mounted on the plunger with its pointed end extending axially toward a pierceable, central portion of the first diaphragm. The other end of the second cylinder is closed and sealed by a puncturable clip and diaphragm assembly having its pierceable portion also axially aligned with the pointed end of the needle.
The first chamber is partially filled with a first medicament, usually in powder form, and the excess space therein is preferably partially evacuated. The second chamber is filled with a second, liquid medicament or vehicle for the first medicament. These medicament components are mixed by partially depressing the plunger so that the pointed end of the needle cannula pierces the first diaphragm. The partial vacuum in the excess space in the first chamber facilitates the flow of liquid from the second chamber through the needle and into the first chamber as the first diaphragm moves toward and into engagement with the second diaphragm, thus mixing the two medicaments. When the second chamber is exhausted and its volume reduced essentially to zero in this manner, an injection may be effected by pressing the puncturable clip and diaphragm assembly against the skin of a patient and further depressing the plunger to the end of its stroke.
This invention also provides similar multichamber devices like the one last described but with the similar provision in the second cylinder of one or more additional, coaxially disposed chambers containing additional, liquid medicament components to be sequentially mixed in a like manner with the first two components prior to making the actual injection.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of a multichamber hypodermic ampoule according to this invention.
FIG. 2 is a cross-sectional view of the ampoule of FIG. 1, the plane of the section being indicated by the line 2-2 in FIG. 1.
FIGS. 3, 4 and 5 are cross-sectional views similar to FIG. 10, but showing component parts of the ampoule in positions attained after initiating a mixing operation, completion of the mixing operation, and completion of an injection operation, respectively.
FIG. 6 is a cross-sectional view of a multichamber hypodermic ampoule according to a further aspect of this invention.
FIG. 7 is a cross-sectional view of a multichamber hypodermic ampoule according to a still further aspect of this invention.
FIGS. 8 and 9 are cross-sectional views illustrating the component parts of the ampoule of FIG. 7 in positions attained at the completion of a mixing operation and after further actuation to ready it for making an injection, respectively.
FIG. 10 is a perspective of a needle which may be employed in combination with devices according to this invention.
FIGS. 11 and 12 illustrate progressive filling and assembly operations to produce the ampoule illustrated in FIGS. 1 through 5.
FIG. 13 is a fragmentary perspective view of an ampoule retaining clip provided in the applicator illustrated in FIG. 9.
FIG. 14 is a bottom end view of an ampoule mounted in the applicator illustrated in FIG. 9.
DETAILED DESCRIPTION OF THE INVENTION Referring now to the drawings, and particularly to FIGS. 1 through 5, amultichamber ampoule 110 is illustrated. Theampoule 110 is adapted to perform a subcutaneous injection and includes a first cylinder 1 1 1 and asecond cylinder 112 of larger diameter, both being preferably made from glass tubing. One end of the first cylinder 111 has a radially extendingannular bead 113 which is received within anannular groove 114 provided in afirst diaphragm 115. The first diaphragm 11-5 is preferably made from rubber and is received with an interference fit within one end of thesecond cylinder 112. This radially compresses this diaphragm and causes it to more tightly embrace thecylinder bead 113.
The other end of the first cylinder 111 is closed by a rubber plunger 1 16 which, together with the first cylinder 111 and thefirst diaphragm 115, defines afirst chamber 117. Theplunger 116 is preferably made of rubber and has an interference fit in the first cylinder.
Entirely enclosed within thefirst chamber 117 is a hypodermic needle (FIG. 10) which is preferably of the type disclosed in U.S. Pat. No. 3,173,206 to Dunmire et al. The illustratedcircular base 119 at the butt end of the needle 1 18 is mounted on the plunger 1 16 so that the needle is in substantial axial alignment with the cylinder 111 and has apointed end 120 projecting downwardly and into thediaphragm 115 in position to be forced through the unpierced remainder thereof. Mounting of theneedle base 119 on theplunger 116 is effected by snapping the peripheral edge of the needle base under an annular lip 26 that is an integral part of the plunger. Flow into the butt end of the needle occurs through anopening 27 in the cannula wall adjacent thebase 119 of the needle.
As will be hereinafter explained in greater detail, thechamber 117 is at least partially filled with apowdered medicament 123 and is partially evacuated. A sliding interference fit between the diaphragm and the inner sidewall of thecylinder 112 aids in sealing thebead 113 within theannular groove 114. Friction between theplunger 116 and wall of the cylinder 111 and resistance of thediaphragm 115 to penetration by theneedle 118, of course, prevent theplunger 116 from prematurely moving toward thediaphragm 115.
The other end of thesecond cylinder 112 is closed by asecond diaphragm 124 and aclip 125. Theclip 125 is cup-shaped and has an innerannular groove 15 in its cylindrical sidewall which snaps over a radially extendingannular bead 12 at one end of thesecond cylinder 112. Theclip 125 also includes abottom wall 125a having acentral aperture 125b therethrough. Thebottom wall 125a has a concave outside surface which includes an outer rim 125s and which tapers upwardly toward theaperture 125b.
The diaphragm is preferably molded from rubber and is shaped to function in accordance with the teachings of U.S. Pat. No. 3,094,988 to Dunmire. It includes an outerannular portion 127, a thick, elongated, centrally located, needle guiding and liquid sealinggland 128 and a relatively thin, flexible, corrugated, intermediate portion 129 connecting the gland and the outer portion to permit relative axial movement therebetween. The gland extends through theaperture 125b in theclip 125. Anaxial needle passage 130 may extend into the upper end of the gland from the inside and terminates short of the opposite, lower end of the gland to form a thin, easilypuncturable wall 131 closing the bottom of the passage.
Thefirst diaphragm 115,second diaphragm 124, andcylinder 112, together, define asecond chamber 132. Thesecond chamber 132 is filled with a liquid medicament in a manner which will hereinafter be explained.
The liquid medicament in the second chamber is mixed with the solid powder medicament in the first chamber prior to injection in a manner which will now be explained. Theplunger 116 is pushed axially toward thefirst diaphragm 115 until theneedle 118 pierces this diaphragm and provides communication through the needle between thesecond chamber 132 and thefirst chamber 117, as shown in FIG. 3. Once communication is established between these chambers, the liquid is drawn upwardly into the first chamber by downward movement of the cylinder 111 andfirst diaphragm 115, together, into engagement with thesecond diaphragm 124, as shown in FIG. 4. At this stage, the pointed end of theneedle 118, which previously pierced thefirst diaphragm 115, has entered thegland 128 of thediaphragm 124.
To ensure that the pointed end of the needle will not be initially extended too far beyond thefirst diaphragm 115 after it pierces that diaphragm, theplunger 116 is provided with a centrally raised portion which extends beyond the end of the cylinder 111 when the ampoule is initially assembled. The raisedportion 140, therefore, extends beyond the end of the cylinder 111 for a distance which substantially corresponds to the thickness of the portion of thediaphragm 115 to be pierced plus the desired extension of the needle beyond thediaphragm 115 during the mixing operation. To perform the penetration operation, therefore, the raisedportion 140 is depressed until its upper or outer end is flush with the top mouth of the cylinder 111, as illustrated in FIGS. 3 and 4.
When theampoule 110 is in the condition illustrated in FIG. 4 and the ampoule has been inverted several times or vigorously shaken as reliable mixing of the medicament components may require (generally not necessary), the ampoule is in a condition suitable for making a subcutaneous injection. To perform the injection, thediaphragm 124 is placed adjacent the patients skin and the plunger is fully depressed until it assumes the position illustrated in FIG. 13. During the plunger depressing step, the needle penetrates thewall 131, and fluid is exhausted from the first chamber through the needle opening 27 (FIG. adjacent theplunger 116 and through the opening in the end of the needle as the needle penetrates the skin and subcutaneous fat of the patient.
Referring now to FIG. 6, an ampoule 158 is illustrated. Theampoule 150 is suited for performing an injection requiring the premixing of two or more liquid medicaments with each other or with each other and with a solid medicament. Theampoule 150 includes afirst cylinder 151 which is preferably made from glass and which has a beadedrim portion 152 at its lower end. Therim portion 152 is received within anannular groove 153 which is provided in a first diaphragm 154. The diaphragm 154 closes one end of thecylinder 151, and the other end of thecylinder 151 is closed by aplunger 155. Aneedle 156 similar to the needle 118 (except for cannula length) is mounted on theplunger 155 similarly to the arrangement of FIG. 2. Apointed end 159 of theneedle 156 is received within apassage 160 in the first diaphragm 154. Theplunger 155,cylinger 151, and the diaphragm 154, together, define afirst chamber 161. As will be hereinafter explained in greater detail, thechamber 161 is partially evacuated during the assembly operation and is at least partially filled with a liquid orpowdered medicament 162.
The first diaphragm 154 is slidably received within asecond cylinder 163. Thesecond cylinder 163 has its upper end closed by the first diaphragm 154 and has its lower end closed by asecond diaphragm 164 and aclip 165 constructed and operating like the previously described similar diaphragm and clip of FIGS. 1-5.
Intermediate diaphragms 167 and 168 are provided in thecylinder 163. Theintermediate diaphragms 167 and 168, thediaphragms 154 and 164, and thecylinder 163, together, define second, third, andfourth chambers 169, 170, and 171, respectively. Thechambers 169, 170, and 171 are filled with different liquid medicaments.
The medicaments contained in the chambers 169-171 are mixed together, and that mixture is in turn mixed with thepowder 162 in the following manner. Theplunger 155 is pushed downwardly until theneedle 156 pierces the first diaphragm 1541 to provide fluid communication between thechamber 169 and thechamber 161. The fluid in thechamber 169 is drawn through thehollow needle 156 and into thechamber 161. After the liquid in thechamber 169 is exhausted in this manner, the diaphragm 154 contacts thediaphragm 167 and thepointed end 159 of the needle enters apassage 172 in thediaphragm 167.Further presend 159 of theneedle 156 then enters apassage 173 in thediaphragm 168 and further pressure on the plunger drives theneedle 156 through thediaphragm 168 to thereby draw liquid from the chamber 171. After the liquid in the chamber 171 is exhausted, thediaphragm 168 contacts thediaphragm 164 and the pointed end of the needle is received within apassage 174 provided in thediaphragm 164.
After the several liquids are mixed with each other and with the material 162 in thechamber 161, the ampoule 158 is in a condition to perform an injection. This injection is performed by placing thediaphragm 164 against the skin of the patient and by depressing theplunger 155 until theplunger 155 contacts the diaphragm 154. It should be appreciated that any number of liquids may be mixed in this manner with or without a powdered medicament, after which the ampoule, with or without an applicator may be used to make a subcutaneous injection in the general manner previously described.
Referring now to FIGS. 7, 8, 9, an ampoule is illustrated, The ampoule 1811 may be employed to mix liquid and powdered medicaments prior to an injection, and may be employed to effect an intramuscular rather than subcutaneous injection. The ampoule 181) is generally similar to theampoule 110 in that it includes afirst cylinder 181 which is closed at one end by arubber plunger 182 and is closed at the other end by afirst diaphragm 183. Theplunger 182 has anenlarged portion 182a which forms a sliding interference fit with the inner sidewall of thecylinder 181. Theplunger 182 is provided with an axially extending reducedupper portion 182b which initially extends beyond thecylinder 181. Aneedle 184 is fixed to theplunger 182 in the same manner previously described, and thediaphragm 183 is slidably received in asecond cylinder 185. Thesecond cylinder 185 is closed at its lower end by asecond diaphragm 186 and aclip 187 constructed and op erating like the previously described similar diaphragm and clip of FIGS. 1-5. Aneedle guard 188 is removably fixed to theclip 187 and extends axially therefrom. Theneedle guard 188 is preferably of transparent plastic, is cup-shaped, and has an open mouth which forms an interference fit with an annular, axially projectingshoulder portion 47 of theclip 187. For purposes which will hereinafter become apparent, theguard 188 is provided with a knurled bottom rib 418.
Thefirst cylinder 181,diaphragm 183, andplunger 182, together, form a first chamber 199 which is evacuated and partially filled with apowdered medicament 191. Thesecond cylinder 185 anddiaphragms 183 and 186, together, form asecond chamber 192 which is filled with aliquid medicament 193.
Themedicaments 191 and 193 are mixed in a manner similar to the mixing procedure set forth with regard to the ampoule 1 111 of FIGS. 1-5. Theplunger 182 is pushed axially until theneedle 184 pierces thediaphragm 183 and provides liquid communication between thechambers 1911 and 192. When such communication is established, thediaphragm 183 moves into engagement with thediaphragm 186, and the parts of the ampoule 1811 assume the positions illustrated in FIG. 8.
To ensure an intramuscular type injection, the needle 1841 must pass through the skin and the surface layers of fat and enter the muscle prior to medicament flow through the needle. Therefore, the chamber is designed so that its volume is greater than the total volume of medicament to be contained therein. Thus, as is illustrated in FIG. 8, there is a space Sp between the liquid level and theplunger 182 when thediaphragms 183 and 186 are drawn together. Prior to effecting an injection, theplunger 182 is further depressed until theplunger 182 contacts the surface of the liquid in thechamber 190. This operation projects the needle 184 a predetermined distance beyond thediaphragm 186, which distance substantially corresponds to the normal maximum depth of the muscle beneath the skin of the patient, and air or gas in thechamber 190 is substantially fully expelled through the needle. This operation is most conveniently performed by placing theneedle guard 188 on a flat surface and pressing theportion 182b downwardly until the top of theportion 182b is substantially flush with the top of thecylinder 181. If desired, the plunger may be depressed in this manner until the appearance of a drop of medicament at the point of the needle (visible through the transparent sidewall of the needle guard 188) indicates the elimination of substantially all air or gas from thechamber 190.
An injection may then be performed by removing theneedle guard 188 and manually applying theampoule 180 against the skin of the patient so that theneedle 184 penetrates the skin and enters the muscle. After this operation, theplunger 182 is completely depressed to inject the medicament into the muscle. A preferred method of effecting an injection, however, is to employ an applicator. As fragmentarily shown herein, such an applicator includes a spring-biasedplunger 50 mounted within acasing 51. An applicator adapted to perform an intramuscular injection includes an elongated, metal, bell-shapedmouth portion 52 which is provided with diametrically opposed inner spring clips 53 or the like (see FIG. 13) which are spot welded to the inner sidewall of theportion 52. Theclips 53 retain theampoule diaphragm clip 187 in the position illustrated in FIG. 9, so that the partiallyadvanced needle 184 is initially recessed in the applicator. With the needle guard attached, theampoule 180 is mounted within the applicator by inserting a pair of diametrically opposed lugs 340 provided on theclip 187 into a cooperating pair ofslots 52a (FIG. 14) which extend axially through a radially inwardly extending flange 5212. This operation is performed by grasping the knurledbottom rib 48 on theneedle guard 188. The ampoule is pushed upwardly into thecasing 51 until the lugs 340 are above the level of the spring clips and is then rotated 90 until thelugs 34a rest on the clips 53 (see FIG. 9). It is desirable to remove theguard 188 after theampoule 180 is mounted in the applicator to prevent contamination of the needle. The needle guard is removed by pulling one portion of therib 48 downwardly while pushing a diametrically opposed portion of the rib upwardly since an axial force applied to the rib may disengage the lugs from their retaining spring clips. After the needle guard is removed, themouth 52 of the applicator is placed against the skin of the patient and the plunger is fired. The applicator spring clips are designed so that they release theampoule diaphragm clip 187 prior to movement of theplunger 182 relative to theampoule cylinder 181. To this end, the springs are designed so that the force required to drive thelugs 34a from their retained position is less than the force required to move theplunger 182 relative to thecylinder 181. In this manner, theneedle 184 is driven into the muscle prior to injection of the medicament. After theneedle 184 enters the muscle, theplunger 182 again moves toward thediaphragm 186 to perform the injection by expressing the medicament through theneedle 184 as it is driven further into the muscle. The injection is complete when the plunger engages the diaphragm.
Referring now to FIGS. 11 and 12, the ampoule is assembled and filled by first attaching theneedle 118 to theplunger 116 and then inserting the plunger in one end of the cylinder 111, as shown in FIG. 11. With the open mouth of the cylinder 111 in an upright position, the cylinder 11 1 is at least partially filled with thepowdered medicament 123 and is subjected to a vacuum during or at the conclusion of the introduction of powdered medicament. While subjected to the vacuum, the first diaphragm 1 15 is applied to the mouth of the cylinder. Thereafter, thesecond cylinder 112 is applied to thediaphragm 115, as illustrated in FIG. 12. Thesecond cylinder 112 is then filled with a liquid medicament, and the remaining components are assembled to provide the ampoule shown in FIGS. 1 to 5.
The invention is not restricted to the slavish imitation of each and every detail set forth above. Obviously, hy-
phragm sealed to and closing one end of said first cylin der, a plunger slidably disposed in the other end of said first cylinder to provide a first chamber between said plunger and first diaphragm, a hollow needle disposed in said first chamber for movement with said plunger toward said first diaphragm and having an open end adjacent said plunger and an opposite pointed discharge end adjacent said first diaphragm, and a powder medicament in said first chamber; a second cylinder axially aligned with said first cylinder and having one end closed by insertion of said first diaphragm therein with a peripheral portion of the first diaphragm in axial sliding engagement with the inner surface thereof, a second diaphragm closing the other end of said second cylinder, said first and second diaphragms and second cylinder, together, defining a second chamber, and a fluid medicament in said second chamber; whereby said fluid and solid medicaments may be mixed preparatory to discharge thereof by first moving said plunger and needle sufficiently toward said first diaphragm to project the pointed end of the needle through said first diaphragm to establish communication between the two chambers and by then moving said first cylinder, first diaphragm, plunger, and needle as a unit toward said second diaphragm to progressively reduce the volume of said second chamber substantially to zero and thereby express said liquid medicament through the needle into the first chamber while bringing said first and second diaphragms substantially into engagement and disposing the pointed end of said needle in position to project the needle through said second diaphragm upon further movement of said plunger toward said first and second diaphragms.
2. A multichamber ampoule according to claim 1, wherein the outer diameter of said first cylinder is less than the inner diameter of said second cylinder.
3. A multichamber ampoule according to claim 1, wherein the volume of said first chamber is substantially equal to the volume of said second chamber.
4. A multichamber ampoule according to claim 1,
xwherein the volume of said first chamber sufficiently exceeds the volume of said second chamber so that the volume of the two medicaments in said first chamber after mixing the medicaments therein is substantially less than the remaining volume of said first chamber, whereby, prior to expelling the mixed contents of the first chamber, said plunger may be further advanced toward said first and second diaphragms to extend a portion of the length of said needle through and beyond said second diaphragm in an exposed condition for projection into a patient to the depth of muscle tissue to be injected, and said plunger may then be moved further toward said first and'second diaphragms to progressively expel the mixed contents of said first chamber through said needle and into said muscle tissue while further advancing said needle into said muscle tissue.
5. A multichamber ampoule according to claim l, in which at least one additional diaphragm is disposed in said second chamber between said first and second diaphragms so as to divide said second chamber into a plurality of smaller chambers, and a corresponding plurality of different liquid medicaments respectively substantially fill said smaller chambers, whereby each of said liquid medicaments, one after another, may be caused to flow through said needle into said first chamber by progressive movement of said first diaphragm, first cylinder, plunger, and needle, as a unit, to bring all of said diaphragms substantially into engagement with one another.