Method and apparatus for the sterilization of ampoules with pharmaceutical liquid therein

Abstract

A method and apparatus for sterilizing liquid containing ampoules having branch parts with microwave irradiation. The ampoules are conveyed to a treating chamber and during irradiation the ampoules are inclined so that liquid does not enter their branch parts and are rotated about their longitudinal axes. Immediately following irradiation, the ampoules may be tilted to cause their branch parts to be filled with heated liquid.

Description

This invention relates to an improved method and apparatus for sterilizing liquid-enclosing ampoules by irradiating said ampoules with microwaves.

In the case of producing a sterile liquid pharmaceutical preparation such as an injectable preparation, generally a sterilizing treatment by an externally heating sterilizing method with heated steam or the like is carried out and, in case the active ingredient is subject to degredation by heating, an aseptic manipulation is rarely adopted.

The present inventors have already discovered a novel sterilizing method comprising irradiating a medicinal liquid in an injectable solution sealed in an ampoule or any sealed container by means of microwaves having a frequency of about 300 to 10,000 MHZ (German Patent Publication No. 2,029,792). According to this method, the medicinal liquid itself is instantaneously heated to a high temperature with various resulting advantages. For instance the medicinal liquid can be quickly and perfectly sterilized simultaneously with the sterilizing action of the microwaves themselves. Moreover, this method minimizes the decomposition of active ingredient pyrogen which has been so far difficult to remove is perfectly decomposed.

However, in this method, it has been experienced that, even if the microwave irradiating condition and ampoule feeding condition are well controlled in a constant condition, in case many ampoules are to be sterilized continuously, some of them will be partially heated and broken by unknown causes and, even in case ampoules are irradiated with microwaves while they are being laterally rolled on a belt conveyer, the temperature of the medicinal liquid in each ampoule will be partially nonuniform.

The present invention is a method and apparatus for sterilizing ampoules which obviates such difficulties. More specifically, the present invention relates to irradiating microwaves while rotating said ampoule as inclined properly so that the liquid may not enter the branch part of the ampoule.

That is to say, according to present invention, by irradiating a liquid-enclosing ampoule with microwaves of about 300 to 10,000 MHZ for a short time while rotating said ampoule which is so inclined that the liquid may not enter the branch part of the ampoule, the liquid temperature difference between the respective parts in each ampoule and between the respective ampoules can be minimized and the contents in the liquid-enclosing ampoule can be effectively sterilized without the above mentioned heretofore unsolved difficulties.

In the sterilizing method of the present invention, the angle of inclination of the ampoule may be more than 45.degree. relative to vertical. In order that the liquid may not enter the branch part of the ampoule, the angle of inclination should be less than about 75.degree. and preferably less than about 70.degree. to vertical though this depends on the kind and capacity of the ampoule and the content of the liquid. It has been confirmed by experiments made by the present inventors that, within the above mentioned range, the larger the angle of inclination, the larger the effect of agitating the liquid in the ampoule by the rotation of the ampoule and the more uniform the liquid temperature distribution in each ampoule. From this viewpoint, the optimum condition is of an angle of inclination of about 60.degree. to 70.degree. .

The number of revolutions of the ampoule may be properly determined by the output of the irradiating microwaves and the irradiating conditions. As in the later mentioned examples, it is desirable to select said conditions so that the ampoule may make several rotations during the irradiation with microwaves.

If the ampoule is irradiated with microwaves under such conditions so that the temperature of the liquid in the ampoule may be about 130.degree.C., preferably 130.degree..+-.5.degree.C., it will be possible to perfectly sterilize the liquid.

The main reason why a uniform definite sterilizing treatment is possible with the present invention is presumed to be as follows from research made by the present inventors.

An ampoule has a barrel part of a large diameter and a narrow branch part. Liquid entering the branch part may not easily extracted due to surface tension, even if the ampoule is inverted. Therefore, if the ampoules are fed at random, the ampoules filled with the liquid in the branch part and those not filled in the branch parts will be present in an irregular mix.

Therefore, it is presumed that, if the ampoules in such random condition are irradiated with microwaves, although the irradiating time, output and ampoule conveying conditions are kept constant, it is impossible to avoid an irregular temperature rise due to the irregular absorption of microwaves in each ampoule which will cause partial overheating in some ampoules and finally the fracture thereof.

If the ampoule is irradiated with microwaves while in an upright position, such unbalance of the effect of the absorption of microwaves caused by the occasional entering of the liquid into the branch part of the ampoule will be avoided. However, according to the research made by the present inventors, it has been confirmed that, in such case, the temperature of the liquid in the bottom part of the ampoule will rise insufficiently and there will be produced a large temperature difference between the upper and lower parts of the liquid which will reach 15.degree.C. even if the liquid is rotated in an ampoule of a small capacity or about 45.degree.C. under stationary conditions. Therefore, it can hardly be adopted as a method of sterlizing ampoules.

Further, in the shape of an ampoule, there is usually a difference of about 10 percent even in the cross-sectional area of the barrel part. There is often a considerable fluctuation in the shape and capacity of the fused part particularly at the tip of the branch part and therefore, so long as such ordinary means of horizontally mounting and conveying ampoules as a belt conveyer is used, even if the internal liquid is forcibly agitated by irradiating the ampoule with microwaves while laterally rolling said ampoule, the liquid will enter the branch part and therefore the nonuniformity of the effect of absorbing microwaves will be unavoidably caused by the nonuniformity of the shape of the branch part.

On the other hand, in the method of the present invention, it is presumed that, as a special ampoule conveying form of rotating ampoules in an inclined position is used, the disadvantage of the liquid entering into the branch part of the ampoule will be avoided and the effect of a uniform temperature will be obtained by the sufficient agitation of the internal liquid.

Further, in the above mentioned method, it has been found that, in case an ampoule is sealed by fusing the tip of said ampoule and is then immediately sterilized, the interior of the branch part of the ampoule will have been sterilized by heating at the time of fusing and therefore there will be no disadvantage although if the interior of the branch part of the ampoule becomes wet due to the tumbling of the ampoule while it is being conveyed or due to any other cause after the sealing of said ampoule, the sterilization of the interior of the branch part of the ampoule may occasionally be imperfect (as shown by the later mentioned examples). In such case, the liquid in the ampoule may be heated by irradiating the ampoule with microwaves for a short time by the above mentioned method and the interior of the branch part of the ampoule may be heated with the conduction heat from the heated liquid by filling the interior of the branch part of the ampoule with said internal hot liquid. Thereby, not only the liquid temperature difference between the respective parts of each ampoule but also the internal liquid temperature difference between the respective ampoules can be minimized and the interior of the liquid-enclosing ampoule can be effectively sterilized.

Such liquid-enclosing ampoule is irradiated with microwaves by being passed through a heating chamber, for example, a wave guide in which microwaves are being radiated.

As a means of conveying liquid-enclosing ampoules while rotating them inclined at the above mentioned angle, there can be utilized, for example, an ampoule conveying or supporting means comprising a conveyer belt, ampoule guiding rail guide inclined by any desired angle and an ampoule drop preventing supporter provided in a position corresponding to the bottom part of the ampoule, a means of pressing the peripheries of each ampoule toward the ampoule advancing direction on said ampoule conveying or supporting means, a means of pulling ampoules in the advancing direction by utilizing the friction with the side of the ampoule or a system of conveying ampoules by properly combining any of these means with a means of pulling ampoules in a direction reverse to the advancing direction. There can be also adopted an ampoule conveying system including a combination of a columnar or cylindrical conveying means such as a screw conveying means having a spirally formed groove on the outer peripheral part with an ampoule supporting guide which can support inclined ampoules.

As a means of filling the branch part of an ampoule with an internal liquid immediately after irradiating the liquid-enclosing ampoule with microwaves, there can be utilized, for example, a system wherein the ampoule is rolled and conveyed by enlarging the angle of inclination of the ampoule by varying the ampoule supporting angle of a conveyor belt, ampoule guiding guide, ampoule guiding rail or an ampoule conveying or supporting means made by properly combining them.

The invention will be further explained by referring the accompanying drawings wherein:

FIG. 1 is a schematic cross-section of a main part of an apparatus embodying the present invention,

FIG. 2 is a schematic side view of FIG. 1,

FIG. 3 and FIG. 4 each is a schematic perspective view showing an ampoule conveying means and a mechanism for adjusting the angle of inclination of ampoules,

FIG. 5 (A), (B) and (C) show the successive positions of the ampoule to be taken during the sterilization process of this invention,

FIG. 6 is a schematic perspective view showing another embodiment of mechanism for adjusting the angle of inclination of ampoules, and

FIG. 7A, B and C each shows the discoloration of a thermopaint applied on the ampoule surface.

The present invention shall be explained in detail with reference to the embodiment shown in FIG. 1 to FIG. 5. In FIG. 1, 1a and 1b are rectangular wave guides connected at one end with respectively independent microwave sources 2a and 2b or common microwave sources and provided at the other end respectively with microwave absorbers 3a and 3b as water loads. In this case, a means of propagating excess microwaves to the adjacent wave guide may be provided instead of the microwave absorber 3a so that the loss of the microwaves may be reduced. Further, the microwave energy may be radiated to the respective wave guides in directions different from each other or in the same direction. In the central parts of both side walls in the lengthwise direction of said wave guide, narrow long slots 4a and 4b (only 4a is shown in FIG. 2) are formed and microwave attenuating means 5a, 5b, 5c and 5d for attenuating the microwave leakage through said slots are provided.

FIGS. 3 and 4 show partly magnified views of a conveying means by which ampoules 6a, 6b and 6c are rolled and conveyed and a mechanism for adjusting the angle of inclination of the ampoules. That is to say, in FIG. 3, the ampoule conveying means consists of a conveyer supporter 7 and a conveyer 8 moving in the direction indicated by the arrow on the supporter. Said conveyer 8 is provided with pressing plates 9a and 9b which contact ampoules on the sides to roll them and drop preventing supporters 10a and 10b for preventing the ampoules from falling off the conveyor.

An ampoule holding part 11a or 11b, a space a little larger than the diameter of the barrel part of an ampoule, is provided between the adjacent pressing plates (for example, 9a and 9b ) so that, when the conveyer 8 is moved in the direction indicated by the arrow by a proper driving means (not illustrated), the ampoule fed into said ampoule holding part may be continuously fed into the above mentioned wave guides 1a and 1b through the slots 4a and 4b (only 4a is shown in FIG. 2) while being laterally rolled by the friction between the side of the ampoule and the conveyer supporter 7. In the respective wave guides, microwave energy is radiated from independent microwave sources or common microwave sources so that the ampoules fed by the above mentioned ampoule conveying means may be successively irradiated with microwaves.

FIG. 4 shows another example of an ampoule conveying means wherein ampoules are laterally rolled and conveyed by a slotted belt conveyer 8 having slots 16a and 16b and a conveyer supporter 7. Said slotted belt conveyer 8 is provided with ampoule drop preventing supporters 10a, 10b, and pressing means 9a, 9b, for pressing the peripheries of each ampoule to roll them in the same manner as in the means shown in FIG. 3. THe slotted belt conveyer 8 continuously conveys and passes ampoules 6a, 6b, through the above mentioned wave guides through the slots 4a and 4b by a proper driving means (not illustrated) so that the ampoules may be fed into the wave guides 1a, 1b, while being laterally rolled by the friction between the peripheries of the ampoule and the conveyer supporter 7. In such case, if the conveyer supporter 7 is continuously moved in a direction opposite to the advancing direction, the number of revolutions of the ampoule will be able to increased so that the temperature of the liquid in the ampoule may be more uniform. In the respective wave guides, microwave energy is radiated from independent microwave sources or common microwave sources so that the ampoules fed by the slotted belt conveyer 8 may be successively irradiated with microwaves.

Thus, when the ampoules pass through the respective wave guides, they will absorb the microwave energy and will be elevated in temperature. When they have passed through all the wave guides, they will have been heated to a fixed temperature. If microwave absorbers 3a and 3b are provided in the end parts of said wave guides, excess microwaves will be absorbed so that the ampoules passing through the other wave guides may be prevented from being overheated and broken by absorbing more than a fixed amount of microwave energy.

The ampoules conveyed by the means shown in FIG. 3 or 4 and heated in the wave guides are then fed to the mechanism for adjusting the angle of inclination of ampoules shown on the left side of FIG. 3. Said ampoule inclination angle adjusting mechanism is provided with an ampoule lower part guiding rod 12 for pushing up the bottom of each ampoules toward the vertical directions, a cut part 13 provided in a part of the conveyer supporter 7 to lower the tip part of the branch of each ampoules and an ampoule branch part supporting rod 14 provided in said cut part 13. When ampoules are continuously fed onto this ampoule inclination angle adjusting mechanism by the above mentioned conveying means, the lower part of the barrel of the ampoule will be vertically pushed up by the ampoule lower part guiding rod 12 and the tip of the branch part of the ampoule will at the same time be lowered below the plane of the conveyer supporter 7 so that the hot liquid in the ampoule may quickly flow into the branch part of the ampoule under gravity to fill said branch part.

The ampoule interior sterilizing process in such case is steppedly shown according to the variation of the inclination angle of the ampoule in FIG. 5. That is to say, in FIG. 5, (A) shows the ampoule fed into the wave guide by the above mentioned conveying means in position for being irradiated with microwaves, (B) shows the ampoule adjusted in the angle of inclination by the above mentioned inclination angle adjusting mechanism immediately after the irradiation with microwaves and where the branch part is filled with the hot liquid in the and (C) shows the ampoule as returned to said angle of inclination after the adjustment of the inclination of the ampoule.

By the way, such mechanism as is shown in the partly magnified view in FIG. 6 may be used as a mechanism for adjusting the angle of inclination of ampoules. That is to say, the inclination angle adjusting mechanism shown in FIG. 6 is of a structure wherein a recess 15 in the form of a gentle slope provided in a part of the conveyer supporter 7 and the same guide rod 12 as is mentioned above is provided in a position in which the lower side of the barrel of the ampoule contacts said recess. Even by using an inclination angle adjusting mechanism of such structure, the hot liquid can be also made to flow into the branch part of the ampoule.

In the sterilizing apparatus of the present invention, ampoules can be passed through a heating chamber or wave guide in which microwaves are being radiated while being rotated as inclined so that the internal liquid may not enter the branch part of the ampoule but may be well agitated in the ampoule when irradiated with microwaves, therefore a uniform microwave absorbing effect can be obtained in each ampoule and the ampoule can be perfectly sterilized without bursting. Further, by using the means in FIG. 3 or 6, the branch part of the ampoule can be filled with the internal hot liquid by enlarging the angle of inclination of the ampoule immediately after the ampoule is irradiated with microwaves. Therefore, even the imperfectly sterilized interior of the branch part of the ampoule can be sterilized with the hot liquid and thus the interior of the ampoule can be perfectly and positively sterilized.

EXPERIMENT 1

Colorless transparent glass ampoules each enclosing 2 ml. of a physiological salt solution were prepared and were painted on the surfaces with a thermopaint which discolors at 110.degree. or 140.degree.C. These ampoules were continuously passed at a conveying velocity of 1.2 m. per minute through a wave guide in which microwaves of an output of 1.3 or 1.5 KW are generated (the ampoules remained in the wave guide 12 seconds/ampoule and 80 ampoules/min.) while being rotated (at 30 rpm) as inclined by 70.degree., 60.degree. or 45.degree. relative to the vertical by using the apparatus shown in FIGS. 1 and 2 (when the conveying means shown in FIG. 4 was used, the residual energy of the microwaves radiated from 2a was propagated by the part 3a, was again radiated from 2b toward 3b and was repeatedly propagated in turn in the same manner so that the ampoule might be irradiated four times in all and the residual energy passing through the last wave guide might be absorbed by a waterloaded absorber at the terminal). The temperature distribution of the entire liquid in the ampoule and the temperature on the surface of the liquid in the ampoule were measured by the degree of the discoloration of the thermopaint and with a surface thermometer. On the other hand, the same ampoules were irradiated with microwaves without being rotated by using a slotless belt conveyer under the same conditions. The results were as shown in Table 1 and FIG. 7. It is shown that, in case the ampoules were not rotated, the temperature of the bottom part of the ampoule was low but the surface of the medicinal liquid in the ampoule was at a moderately high temperature and the temperature of the liquid in the ampoule was nonuniform. On the other hand, it is shown that, in case the ampoules were rotated when inclined, the entire medicinal liquid in the ampoule was uniformly heated. In FIG. 7 the hatched part indicates that there was no discoloration of the thermopaint. The data for FIG. 7 are as follows: FIG. 7-A Not rotated, Microwave output 1.3 KW, Thermopaint 110.degree.C., Liquid surface temperature 132-133.degree.C. FIG. 7-B Not rotated, Microwave output 1.5 KW, Thermopaint 140.degree.C., Liquid surface temperature 145-146.degree.C. FIG. 7-C Rotated, Microwave output 1.3 KW, Thermopaint 110.degree.C., Liquid surface temperature 125-127.degree.C.

Table 1 __________________________________________________________________________ Thermopaint Angle of Liquid discoloring Output inclination of surface Thermopaint discoloration temperature (KW) the ampoule temperature (.degree.C.) (Degrees) (.degree.C.) __________________________________________________________________________ 70 FIG. 7A (below 110.degree.C. in the 110 1.3 60 132 - 133 bottom part of the ampoule) Not 45 rotated 70 FIG. 7B (below 140.degree.C. in the 140 1.5 60 145 - 146 bottom part of the ampoule) 45 70 Uniformly discolored (above 110 1.3 60 125 - 127 110.degree.C. in the entire ampoule) 45 FIG. 7C (below 110.degree.C. in the bottom part of the ampoule) Rotated 70 Uniformly discolored (above 110 1.5 60 132 - 133 110.degree.C. in the entire ampoule) 45 __________________________________________________________________________

EXPERIMENT 2

Two groups of 2 ml.-capacity colorless transparent glass ampoules each enclosing 2 ml. of a physiological salt solution were used. In one group, the difference in the shape of the ampoule particularly in the capacity of the branch part was quite small. In the other group, no such selection was made. By using the same apparatus as in Experiment 1, each ampoule was heated to an average of 120.degree.C. by being continuously passed at a conveying velocity of 1.2 m. per minute through a wave guide in which microwaves of an output of 1.5 KW were being radiated while the ampoule was laterally rolled (at 30 rpm) while horizontal (the ampoules remained in the wave guide 12 seconds/ampoule and 80 ampoules/minute). The temperature in the central part of the surface of the medicinal liquid in each ampoule was measured with a surface thermometer. As a result, it was found that, in the tested group in which the shapes of the respective ampoules were uniform, the fluctuation of the liquid surface temperature was small (about .+-.2.degree. to 3.degree.C.) but that, in the group of the random samples, the liquid surface temperature difference in each ampoule was considerable (reaching .+-.7.degree. to 8.degree.C.) and the influence of the nonuniform shape each ampoule, particularly of the difference in the capacity of the branch part was large.

EXPERIMENT 3

A bacterial body of bacillus Subtilis PCl-219 was suspended in a phosphoric acid buffer solution (of a pH of 7.2) consisting of an aqueous solution of 1.77 percent potassium phosphate and an aqueous solution of 3.56 percent sodium phosphate. The suspension was enclosed in a 2 ml. capacity colorless transparent ampoule. Before heating, the ampoule was inverted to wet the interior of the branch part of the ampoule to be tested. By using the apparatus shown in FIGS. 1 and 2 (wherein the conveying means shown in FIG. 3 was used), the above mentioned ampoules to be tested were inclined by 70.degree. and were continuously passed at a conveying velocity of 0.99 m. per minute through a wave guide in which microwaves of an output of 1.67 or 1.88 KW were being radiated (the ampoule remained in the wave guide 14.5 seconds/ampoule and 33 ampoules/minute) while being rotated (at 25 rpm) and were then immediately inverted so that the branch part of each ampoule might be filled with the hot liquid for 3 seconds as a treated group. Alternatively, the same ampoules were merely irradiated with microwaves under the same conditions except the above prewetting treatment, as a control group. The sterilizing effects in the ampoules of the treated group and control group were investigated by the sterility testing method of the Japanese Pharmacopoeia. The results were as shown in Table 2. (In the table, (-) represents a pass in the sterility test and (+) represents a failure in the sterility test. Further, in the table, the temperature of the liquid in the ampoule was measured after the ampoule was inverted immediately after it was irradiated with microwaves in the treated group, and was measured immediately after the ampoule was irradiated with microwaves in the control group.)

Table 2 ______________________________________ Temperature Experiment Output Sterility of the liquid No. (KW) test in the ampoule (.degree.C.) ______________________________________ 1 - 2 - 3 1.67 - 121 - 122 4 - Treated 5 - group 6 - 7 - 8 1.88 - 132 - 133 9 - 10 - 11 + 12 + 13 1.67 + 121.5 - 122 14 + Control 15 + group 16 + 17 + 18 1.88 + 135 - 137 19 + 20 + ______________________________________

EXAMPLE 1

Colorless transparent glass ampoules each filled with 2 ml. of a physiological salt solution were continuously passed at a conveying velocity of 1.2 m. per minute through a wave guide in which microwaves of an output of 1.3 KW were being radiated (the ampoules remained in the wave guide 12 seconds/ampoule and 80 ampoules/minute) while being laterally rolled (at 30 rpm) as inclined by 70.degree. to the vertical with the same apparatus as in Experiment 1. The temperature reached in the solution in each ampoule due to the irradiation with microwaves was within the range of 122.5.degree. .+-. 2.5.degree.C. and no ampoule was broken. All the ampoules passed the sterility test defined by the Japanese Pharmacopoeia.

EXAMPLE 2

Injectable distilled water preparation was prepared by the same treatment as in Example 1 but substituting 3 ml. of distilled water for 2 ml. of the physiological salt solution in Example 1. The temperature reached in the medicinal liquid in each ampoule and the sterility test results in this example were within exactly the same ranges as in the preceding example.

EXAMPLE 3

An injectable preparation was prepared by the same treatment as in Example 1 except that an aqueous solution of 1.0 percent sodium carbazochromesulfonate was substituted for the physiological salt solution and the output of microwaves was 1.5 KW.

The temperature reached in the medicinal liquid in each ampoule in this example was within the range of 120.degree. .+-. 3.degree.C. and no ampoule was broken. All the ampoules passed the sterility test the same as in Example 1.

EXAMPLE 4

Colorless transparent glass ampoules each filled with 2 ml. of a physiological salt solution for injection were continuously passed at a conveying velocity of 1.2 m. per minute through a wave guide in which microwaves of an output of 1.3 KW were being radiated (the ampoules remained in the wave guide 12 seconds/ampoule and 80 ampoules/minute) while being laterally rolled (at 30 rpm) and inclined by 70.degree. to the vertical with the same apparatus as in Experiment 3. Then the ampoules were adjusted to an angle of inclination of 100.degree. by using the ampoule inclination angle adjusting mechanism shown in FIG. 3 and were filled with the hot liquid in the branch parts for 3 seconds.

The temperature reached in the medicinal liquid in each ampoule due to the irradiation with microwaves was within the range of 122.5.degree. .+-. 2.5.degree.C. and no ampoule was broken. All the ampoules passed the sterility test defined by the Japanese Pharmacopoeia.

EXAMPLE 5

Injectable distilled water preparation was prepared by the same treatment as in Example 4, but substituting 3 ml. of distilled water for 2 ml. of the physiological salt solution in Example 4. The temperature reached in the medicinal liquid in each ampoule and the sterility test results in this example were within exactly the same ranges as in the preceding example.

EXAMPLE 6

An injectable preparation was prepared by the same treatment as in Example 4 except that an aqueous solution of 1.0 percent sodium carbazochromesulfonate was substituted for the physiological salt solution in Example 4 and the microwave output was 1.5 KW.

The temperature reached in the medicinal liquid in each ampoule in this example was within the range of 123.degree. .+-. 3.degree.C. and no ampoule was broken. All the ampoules passed the sterility test the same as in Example 4.

Claims

What is claimed is:

1. A method for sterilizing liquid-containing ampoules having branch parts which comprises the steps of: inclining each ampoule containing a liquid to an angle of inclination so that the liquid does not enter the branch part of the ampoule; rotating the ampoule about its longitudinal axis while in the inclined position; and irradiating said ampoule with microwaves, so that the liquid does not enter into the branch part of the ampoule during the irradiation process.

2. A method for sterilizing liquid-containing ampoules as claimed in claim 1, wherein each ampoule completes several rotations during the microwave irradiation process.

3. A method for sterilizing liquid-containing ampoules as claimed in claim 1, wherein the ampoule angle of inclination is from about 45.degree. to 70.degree. relative to vertical during the microwave irradiation step.

4. A method for sterilizing liquid-containing ampoules as claimed in claim 1, wherein the ampoule angle of inclination is from 60.degree. to 70.degree. relative to the vertical during the microwave irradiation step.

5. A method as claimed in claim 5 further comprising the step of adjusting the inclination angle of the ampoule supporting angle of a conveying means after the microwave irradiating step so that the branch part of the ampoule is thereafter filled with the heated liquid.

6. An apparatus for sterilizing liquid-containing ampoules comprising a microwave source, a heating chamber connected with said microwave source, a conveying means operatively positioned for passing liquid-containing ampoules through said heating chamber, means associated with said conveying means for inclining said ampoules so that the liquid may not enter the branch parts of the ampoules while said ampoules are passing through the heating chamber, means cooperating with the conveying means for rotating said ampoules and means for adjusting the angle of inclination of said ampoules after the ampoules pass through the heating chamber, thereby filling branch parts of the ampoules with internal hot liquid and positioned on a part of said conveying means extending beyond said heating chamber.