US2251527A - Syringe and ampoule - Google Patents

Description

Aug. 5, 1941.

A. E. SMITH 2,251,527

SYRINGE AND AMPOULE 2 Sheets-Sheet 1 Filed Nov. 3, 1933 INVENTOR. HRTHuR E. 5M1 T'H.

ATTORNEY.

Patented Aug. 5, 1941 UNITED STATES PATENT, OFFICE SYRINGE AND AMPOULE 7 Arthur E. Smith, Los Angeles, Calif.

Application November 3, 1933, Serial No. 696,506

10 Claims.

This invention relates to ampoule syringes.

The general object is to provide a novel syringe construction embodying a removable ampoule, wherein novel means is provided to enable a solution having a correct pH constituency to be prepared.

Another object is to provide a novel ampoule including a closure with a medicinal tablet arranged in the closure and adapted to be discharged therefrom into a vehicle to form a solution.

Another object is to provide a syringe having an ampoule therein wherein the ampoule includes a closure which has a medicinal tablet sealed therein and wherein the syringe includes means to cause the tablet to be exposed.

A further object of my invention is to provide a novel closure for containers.

Other objects and the advantages of this invention will be apparent from the following description taken in connection with the accompanying drawings wherein:

Fig. 1 is a central, longitudinal view through a syringe and ampoule embodying the features of my invention;

Fig. 2 is an enlarged fragmentary, central, sectional view showing my improved ampoule closure;

Fig. 3 is a fragmentary, central, longitudinal, sectional view showing a portion of the ampoule and syringe barrel;

Fig. 4 is a view similar to Fig. 2 showing a modification of my invention;

Fig. 5 is a view similar to Fig. 4 after the projec-tion has been removed from the ampoule closure;

Fig. 6 is a fragmentary, central, sectional view showing a modified type of ampoule closure;

Fig. 7 is a view similar to Fig. 6 showing the ampoule;

Fig. 8 is a fragmentary sectional view of a modified type of movable closure or piston member;

Fig. 9 is a section showing the closure of Fig. 8 in another position;

Fig. 10 is a view similar to Fig. 8 showing a further modification; and,

Fig. 11 is a sectional view taken partly in elevation showing another modification.

This invention relates to means for producing from stable drugs a fresh ready-to-use solution for administration by hypodermic injection.

There are a number of important medicinal compounds which are unstable in stock solution and which after varying time intervals undergo local anesthetics.

deterioration, thereby altering or destroying their original medicinal qualities. For example, among the well-known drugs which undergo deterioration in stock solution contained in ampoules are: sodium iodide, potassium iodide, calcium gluconate, sodium salicylate, neo-salvarsan and procain-epinephrln.

Pharmaceutical manufacturers have experienced difliculty from discolored and disintegrated compounds in solution form. This is an added source of expense to the pharmaceutical manufacturer and trouble to the druggist, because the physician will not administer compounds which are discolored for fear of toxicity and loss of the original medicinal activity of the drug or drugs.

Numerous methods have been evolved to manu facture and dispense unstable compounds which would retain their medicinal activity and freshness, but such methods have proved futile and, at the present time, a canvass of the various pharmaceutical houses and retail drug stores would disclose the information that considerable trouble is experienced with many unstable drugs which are marketed in solution form in ampoules.

For the purpose of explanation relating to my invention, I may use, as an example, two medicinal compounds which will illustrate the usefulness and advantage of my invention. The first example is that of neo-salvarsan. As is wellknown, this is one of the arsphenamine compounds, administered by intravenous injection, in the treatment of syphilis. A solution of neosalvarsan must be made freshly at the time of intravenous injection, because it is very unstable in soluble and should be injected into the blood stream without the necessity of mixing it in two receptacles, as is common practice. The solution is injected from the original container as will be later explained.

The second example I desire to use in explaining the operation of this invention is in the use of In order to obtain emcient results, a local anesthetic should possess certain characteristics, such as: The solution should be isotonic; it should have a pH similar to that of the living cells and tissue fluids; it should produce rapid and profound anesthesia; it should be nontoxic; it should be readily absorbed by the tissues; it should not produce irritations nor cause postoperative discomfort or pain.

In the following I describe a technic and package which makes possible the compounding of a ready-to-use buffered procain-epinephrin solution which possesses approximately the same pH as that of the living cells and tissue fluids, and is isotonic.

The pH of living cells and tissue fluids is approximately 7.4 which is slightly alkaline. A pH 7 solution, as is well known, is neither acid nor alkaline and any amount above 7 represents alkalinity and, below, acidity. Therefore, if a local anesthetic solution possesses a pH of 7 or slightly above, it is not necessary for a chemical change to take place in the tissue fluids and cells in which it is injected. For example, a solution possessing a pH of 4, which is acid, is changed chemically by the tissue fluids and cells to approximately pH 7. Any solution below pH 7 being slightly acid when injected into the tissues causes a chemical change to take place which requires additional time for anesthesia to be produced.

This chemical change required to change a pH solution of 4 to one of 7 causes discomfort and pain to the patient. In order to prepare a buffered anesthetic solution, it is necessary to add a buffer salt, such as sodium carbonate, potassium carbonate, sodium lactate or sodium phosphate. The ready-to-use local anesthetic procam-epinephrin solution such as are sold in ampoules possess a pH of from 3.5 to 5.5 and must maintain a pH of 3.5 to in order to retain stability. For example, if a buffer is added to the vehicle to produce a pH of 6.14 there commences immediate decomposition of the procam hydro-chloride into para-amin-benzoic acid and, in addition, decomposition of the epinephrin by oxidation. The decomposition of such a solution results in acidity and toxicity and causes the pH to change to a pH of 4 to 5 which is within the stability range.

Therefore, it will be seen that if a buffer salt is added to a stock or ready-to-use local anesthetic solution at time of manufacture and as sold in ampoules it stimulates or enhances chemical change to produce a high potential acid solution. The injection of such a solution into the tissues not only creates post-operative pain and discomfort to the patient, but the original medicinal activity of procain and epinephrin hydrochlorides have been altered or destroyed. A local anesthetic solution containing a buffered salt, such as sodium phosphate, potassium carbonate, sodium lactate or calcium carbonate must be made fresh and injected immediately upon preparation.

In other words, it must be injected immediately following the mixing of procain and epinephrin to the buffered vehicle. A stock buffered procamepinephrin local anesthetic solution possesses a highly potential acidity to such an extent that it is a tissue irritant and, when injected, may cause after-pain and sloughing or delayed regeneration of the tissues. The anesthetic agent, namely, procain hydrochloride, the vaso-constricting agent, namely, epinephrin hydrochloride must not be added to the vehicle containing the buffer salt and Ringer chlorides until the time it is to be injected into the patient.

The ideal local anesthetic vehicle has a pH of 7.2 and is isotonic. It is rendered isotonic by the addition of Ringer constituents and made pH 7.2 by employing a buffer salt. Procain and epinephrin hydrochlorides are added in the desired amounts to make the desired percentage solution.

My invention makes possible the preparation of a local anesthetic solution which is neutral or slightly alkaline in reaction, fresh, the full effect of the medicinal activity is obtained and no post-operative change in the tissues is caused, which eliminates discomfort and pain to the patient caused by the injection of a solution that is not isotonic and possessing a low pH.

Referring now to the accompanying drawings by reference characters, I have shown my invention as embodied in a syringe indicated generally at In. As shown, this syringe includes a barrel ll having a front member [2 thereon at one end. The barrel is closed at the other end by a cap l3 which has a plunger I4 movable therethrough. The plunger M has a head l5 thereon which is normally urged forward by a disk 15' which is engaged by a spring It. The spring I6 is surrounded by telescopic segments I1, as clearly shown in the drawings.

Within the barrel II I show one embodiment of my improved ampoule which is indicated generally at I8. This ampoule is preferably made of glass and is cylindrical with ends at right angles to the axis of the ampoule.

In the rear end of the ampoule, I provide a stopper I9. This stopper is preferably made of a good grade of rubber and is adapted to be pushed forward by the head I5 of the plunger to act as a piston to expel the contents of the ampoule as will be presently understood. In the front end the ampoule is provided with a closure indicated at 20. This closure is preferably made of rubber and in its original state is shown at Fig. 2 as comprising a body having a forwardly projecting tip -2| thereon. The body of the closure 20 is provided with a central cylindrical hole 22 which merges into a hole 22' which may taper. The hole 22 opens into a pair of coaxial recesses 23 and 24 which are cylindrical and of different diameters to provide shoulders at the lower edges thereof.

0n the innermost shoulder I seat a disk 25 preferably made of Celluloid or other inert material and on this Celluloid disk I place a medicinal tablet, pellet, capsule, etc., 26. This is followed by a second Celluloid or other disk 21, and a wax 21' covers the disk 21 to seal the parts leak-proof. The disks 25 and 21 are of a greater diameter than the recess which they fit so that each tightly engages with the walls of the recess with which it is associated to prevent accidental removal thereof. The closure is provided with an outwardly directed shoulder 28 and with a bevelled wall 29 which acts in con junction with the end of the ampoule to provide a V-shaped annular groove.

The projecting tip 2| is provided with a V- shaped recess 30. A coating 3| of wax or other sealing material is placed over the ampoule closure and tip to seal the parts.

In use the tip 2| is removed by cutting at or near the groove 30 after which the ampoule I8 is placed in the barrel as shown in Fig. l. The front member I2 is provided with a sharp circumferentially inwardly extending bead 32 which engages the end of the closure 20 and forces the shoulder 28 against the end of the ampoule and maintains the parts in fluid tight engagement. The front end of I2 is provided with a tube 33 which is provided with discharge apertures 34 and is of considerably less diameter than the diameter of the hole 22 so that the tube enters the hole without touching the walls thereof and thereby avoids mishaps.

This tube 33, when the ampoule is inserted, after passing through the hole 22 forces the disk 25, the tablet 26 and the disk 21 out of their associated recesses. The ampoule barrel contains a suitable solvent or vehicle for the medicinal contents of the tablet 26 and when the tablet is pushed into the vehicle by breaking the seal by means of the tube 33, a fresh local anesthetic solutionis prepared, which possesses a pH of 7.2, is isotonic and contains the desired amount of the local anesthetic agent procain and the vaso-constricting agent epinephrin.

As stated, in practice, stock solutions have been found unsatisfactory for anaesthetic work and although the solutions now placed in ampouies have been made to stand up without disintegration or discoloration for many months, yet I have found that by preparing an ampoule so that a fresh solution can be made for each injection, a better result can be obtained since the pH constituency can be regulated to meet the approved practice.

In Figs. 4 and 5 I show a modification of my invention wherein the ampoule 49 is provided with a rubber closure 4| similar in all respects to the closure 20 previously described except that the hole 42 terminates in a wall 43 which when the tip 44 is severed leaves a thin diaphragm 45 as shown in Fig. 5. This diaphragm 45 will be punctured by a member similar to the tube 33 when the ampoule is used.

The hole 43 communicates with a chamber 46 in which a tablet 41 is arranged. The disc 25 is omitted but a sealing disc 48 similar to the disc 21 is employed and this is covered by a wax seal 49.

In Figs. 6 and 7 I show a further modification of my invention wherein the ampoule 50 is provided with a closure 5| which is shown as similar in all respects to the closure 28 which has been previously described with the exception that the hole 52 extends from the tip entirely through the body of the ampoule.

The movable closure 53 is provided with peripheral arcuate grooves 54 in which wax may be inserted to reduce friction. This closure 53 is provided with a central hole 55 which communicates with coaxial chambers 56 and 51. A feather edge 58 is provided at the bottom of the closure. The hole 55 at its upper end, is sealed by a rubber diaphragm 59 and at its lower end by a Celluloid disc 66. A tablet 6| is arranged in the smaller chamber and is sealed therein by a second disc 62 which is in turn sealed by wax 63.

In operation the ampoule 50 after the tip 65 is removed is inserted in a syringe barrel which has an ampoule engaging member 66 which urges the ampoule forward to make a fluid tight seal. The syringe barrel includes a plunger 61 on which a head 68 is arranged to engage the closure 53 and move it forward. Prior to this engagement however the end of the plunger will pierce the thin diaphragm 59 and will advance through the hole 55 forcing the discs 60 and 63 together with the tablet 6| into the vehicle in the ampoule.

In Fig. 8 the ampoule 69 has a movable piston therein indicated generally at 69. This piston is made of two parts comprising an upper member 69' and a lower member 69". These members are provided with aligning recesses 69*. The upper recess is closed by a diaphragm 69 and the lower recess is closed by a diaphragm 69 A tablet member ID is placed in the recess between the members 69 and 69 In use a plunger ll perforates the diaphragm 69 then pushes the tablet through the diaphragm 69 into the vehicle. The plunger will include means on its end face. 811011 is a head 12, to seal the aperture produced when the diaphragms are removed.

In Fig. 10 I show an ampoule 18 which has a piston 14 movably mounted therein. This piston 14 is provided with a central bore 16 which is closed at its upper end by a diaphragm I6. A stiff pin TI is loosely mounted in the bore. A tablet 18 is arranged in a recess I9 at the end of the piston opposite the diaphragm 16. A disc engages the wall 8| to seal the tablet 18 in place.

In use a. plunger 82 moves within the ampoule l3 and engages the diaphragm 18 without puncturmg the same and moves downwardly moving the pin 11 and causing the pin 11 to force the tablet l8 and the disk 88 into the vehicle in the ampoule.

In Fig.11 I show a container which may be any type of receptacle, at 85. This container is shown as provided with a neck 86 which has a peripheral bead 81 thereon, and has a rubber closure member, indicated at 88, thereon. This closure member includes an inner skirt 89 and an outer skirt 90 which engages the neck 86 therebetween.

The closure is provided with a cavity 9| in which a capsule or tablet 92 is placed. The cavity is sealed by a disc 93 which engages the wall of the cavity. The closure is provided with a hole 94, the lower end of which is closed by a diphragm 95 and the upper end of which is open to receive a pin 96 having a head 91 which is engaged by a top 98 of a metal cap which is provided with a skirt 99.

The skirt cap is of a size to slide on the outer periphery of the outer skirt 90. The skirt 99 and the skirt 90 may be covered with a sealing matenal such as wax N10, or other material.

In use the top 98 of the cap is pressed downwardly forcing the pin 96 through the diaphragm 95 thus engaging the capsule or tablet 92 and causing it to force the disc 93 and the capsule into the vehicle in the container 85. After this is done the cap 99 and the pin 96 are removed and the material suitably withdrawn from the container 85 after which the pin is thrown away. The cap 98 may then be filled with gauze which has been saturated in alcohol and replaced if all of the solution has not been used.

From the foregoing description it will be apparent that I have invented a novel type of ampoule syringe which can be economically manufactured and which is highly efficient in use.

Having thus described my invention, I claim:

1. In a container closure, a hollow body having a recess therein opening from one end thereof, a d1sc at one end of said recess, a tablet adjacent said disc, a second-disc adjacent said tablet and spaced from the first disc, means whereby said discs are held in place, said closure having a hole therein leading to the other end of said recess.

2. In a container closure, a cork having a hole therein, said cork being made of flexible material and including a chamber communicating at one end with the hole and having the other end open, a removable disk in the chamber adjacent the hole, a second disk in the chamber and spaced from the first disk, a medicinal preparation between said disks, said seccnd disk being spaced from the end of the cork.

3. A syringe including a barrel, an ampoule in said barrel, a cork in said ampoule in one end thereof and including means adapted to make a fluid tight engagement with the forward end of the barrel, a cork in the other end of the ampoule and movable therein, one of said corks having a hole therein and having a chamber communicating with said hole, said chamber opening into the interior of the ampoule and being of larger diameter than the hole to provide a shoulder, a disk engaging said shoulder, a second disk in said chamber and spaced from said first disk and a medicinal preparation between said disks, said syringe including a member projecting into the barrel and of less size than said hole and adapted to pass into and through said hole and into the chamber to force the tablet from the chamber into the ampoule.

4. For use with a hypodermic syringe comprising a barrel having a hollow tube mounted at one end and extending into the barrel, a plunger mounted on the other end, a discardable cartridge adapted to be received in the barrel, said cartridge comprising a receptacle having a piston plug at one end adapted to be operated by said plunger, a plug at the other end of said receptacle, said second plug having a chamber therein, a closure sealing one end of said chamber, said plugs defining a second chamber adapted to hold liquid, means sealing the other end of said plug chamber and accessible for engagement by said tube, a medicament in said first chamber, a closure sealing the open end of said first chamber and adapted to be displaced upon the inward movement of the inwardly extending end of the tube thereby to combine the medicament and liquid.

5. The method of preparing for and making a hypodermic injection which consists in loading a cartridge with a medicament and a desired quantity of a solvent therefor, and segregating said medicament and solvent, then inserting the cartridge into a syringe, and, by the act of inserting the cartridge into the syringe, efiecting the union of the medicament and the solvent, and then ejecting the contents of the syringe from the syringe by forcing inwardly a closure for the end of the cartridge.

6. In combination, a syringe having a plunger, a cylindrical body and a hollow tube with its inner end projecting into the space within the body, and a discardable cartridge adapted to be received within said body and when so received to constitute the cylinder and piston of the syringe, said cartridge consisting of a receptacle adapted to contain a solvent or carrier [or a medicament, a flanged non-metallic plug adapted to close one end of said receptacle and provided with an axial chamber open to the inside of the receptacle and adapted to contain a medicament, a closure sealed in the open end of the chamber, said closure being in position to be displaced by the inwardly projecting end of the tube as a necessary result of the act of loading the cartridge into the" syringe body and thereby to combine the medicament and carrier, the opposite end of the receptacle being closed by an unflanged plug adapted to be displaced by the inward movement of the plunger and thereby to act as a piston for ejecting the mixture within the receptacle through the tube.

7. A hypodermic injecting device comprising, in combination, a syringe having a plunger, a barrel and a hollow tube, the parts being adapted to be operated to present an open upper end on the barrel, said tube being positioned with its inner end projecting into the barrel, and a cartridge adapted to' be received within the open end of the barrel and when so received to constitute the cylinder and piston of the syringe, said cartridge consisting of a receptacle of substantially uniform diameter from end to end and adapted to contain a carrier .or diluent for a medicament, a flanged non-metallic plug adapted to close one end of the receptacle and provided with a chamber one side of which is open to the inside of the receptacle, said chamber being adapted to contain the medicament, a closure sealed in the open side of said chamber, said closure being adapted to be displaced by the inwardly projecting end of the tube as a result of placing the cartridge in operative position in the barrel of the syringe, whereby said chamber is opened and the medicament is permitted to intermix with the diluent, the piston end of the receptacle being closed by an unfianged plug adapted to be displaced by the plunger and thereby to act as a piston for ejecting the mixture within the receptacle through the tube.

8. The combination with a syringe including a. cylindrical body, a plunger, and a hollow tube having its inner end projecting into the space within the body, of a discardable cartridge adapted to be received within said body and when so received to constitute the cylinder and piston of the syringe, said cartridge comprising a receptacle adapted to contain a solvent or carrier for the medicament, a non-metallic plug adapted to close one end of the syringe and provided with an axial chamber open to the inside of the receptacle and adapted to contain a medicament, a disk overlying the inner face of the non-metallic plug and sealed thereto over a relatively small area for closing the axial chamber but adapted to be readily displaced therefrom by engagement of the inwardly projecting end of the tube as a necessary result of the act of loading the cartridge into the syringe body and thereby to combine the medicament and carrier or solvent, the opposite end of the receptacle being closed by a plug adapted to be displaced by the inward movement of the plunger and thereby to act as a piston for ejecting the mixture within the receptacle through the tube.

9. For use with a syringe having an inwardly projecting hollow tube on its needle receiving end, a cartridge consisting of a body provided with a closure adapted to be positioned adjacent the needle receiving end of the syringe, a piston closure at the other end of the body, the inner surfaces of said closures combining with the inner surfaces of the body member to form a primary chamber, a secondary chamber formed in said first named closure and a plug displaceable by contact with said syringe tube and positioned in said first named closure member for sealing the said secondary chamber.

10. The method of preparing for and making a hypodermic injection which consists in loading a cartridge with a medicament and a desired quantity of a solvent therefor, and segregating said medicament and solvent, then inserting the cartridge into a syringe, and causing a member on the syringe to eifect the union of the medicament and the solvent, and then ejecting the'contents of the cartridge from the syringe by forcing inwardly a closure for the end of the cartridge.

ARTHUR E. SMITH.

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