JP2004148106A - Artificial nipple for experimental animal - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an artificial nipple which is suitably used when a liquid feed or a testing solution can be voluntarily and orally given to an experimental animal with a need for feeding such as mouse infants, and to provide a feeding bottle suitably used in combination with the nipple, a liquid feeding device made in combination with those, and a method for feeding liquid. <P>SOLUTION: The artificial nipple has a replaceable fine tube part therein and a structure preventing a liquid from piling up in the nipple, which is formed by filling the nipple part other than the nipple tip part and the fine tube part with an elastic member or is formed by integrating the elastic member with the outer wall of the nipple. The feeding bottle has a replaceable cylinder shape part inside. Preferably, the feeding bottle has a check valve inside. The liquid feeding device for the experimental animal is prepared by combining the artificial nipple with the feeding bottle. The method to feed the liquid to the experimental animal includes varying sizes and shapes of the artificial nipples according to conditions of the experimental animals and replacing them, when using the liquid feeding device. <P>COPYRIGHT: (C)2004,JPO

Description

  The present invention is preferably used in combination with an artificial nipple and its nipple which are preferably used when a test liquid such as a liquid feed or a medicinal solution is spontaneously orally given to a laboratory animal requiring nursing such as a mouse infant. The present invention relates to a baby bottle designed to be used, a liquid supply device for laboratory animals comprising the artificial nipple and the baby bottle, and a method of using the same.

  It is essential to acquire data using experimental animals in development research and various basic researches on pharmaceuticals, nutritional foods, specific functional foods, and the like. Among them, infants such as mice and rats are equivalent to premature infants whose eyes and ears are not open in humans, and their organs are not mature, so they are extremely sensitive to drugs, etc. We can expect acquisition.

The mainstream method for feeding milk and the like to experimental animals requiring nursing such as infants is to forcibly feed the gastrointestinal tract using a gastric tube and a catheter. This is considered to have been adopted because it is necessary to control the dose, the administration interval, and the like when administering milk, a test solution, or the like according to the purpose of the study. However, these methods cannot avoid invasion to the living body, such as abrasion of the pharynx and esophagus in a gastric sonde, and generation of a wound accompanying the wearing of a catheter. As a result, there is a high possibility that the data of each experimental animal will vary due to inflammation caused by damage to the visceral wall or the like. In addition, if it is necessary for experimental purposes that laboratory animals voluntarily ingest milk or test liquids, such as in the development of special-purpose milk, the gastric sonde method or catheterization method, which is a compulsory administration method, cannot be applied. There were also problems. Even for non-research purposes, the use of gastric probe and catheterization in infants of mice and rats weighing less than 3 grams, as described above, may cause the soft pharynx, esophagus, and stomach wall to be damaged. It is particularly likely that the needle will cause damage.

Therefore, the use of mouse or rat babies for the development of drugs or milk for specific uses such as milk for premature babies can be expected to provide highly accurate data, while milk and test solutions are spontaneously applied to mouse and rat babies. There has been virtually no method of single or repeated quantitative administration safely orally.

In the process of developing a method of administering a liquid feed to an experimental animal, the present inventors have already conducted an experiment in which the experimental animal can drink milk via an artificial nipple or the like at his own will without using a stomach sonde or the like. We have developed and reported an automatic artificial nursing device for animals. For example
.

The feature of the automatic artificial breastfeeding device is the structure of the artificial nipple. The artificial nipple has a double structure so that the milk does not leak when the baby is not drinking milk, and the outer nipple has a cross cut at the tip. The inner nipple has four slits on the side. Furthermore, a structure is adopted in which an injection needle having a diameter of 24-26 G, excluding a needle tip, is inserted into a nipple, and a combination of these structures is intended to prevent leakage of milk and control flow.

This automatic artificial nursing apparatus is also designed so that the experimental animal can spontaneously suck into the artificial nipple and ingest liquid feed or the like orally as in the present application. However, this apparatus has the following problems.
1) It is mainly intended for rat babies, and cannot follow the growth of smaller mouse babies.
2) With this device, it is not possible to easily supply a test liquid or the like in such a form as to supply milk to a baby by hand if necessary. Therefore, with this device, it was possible to feed the rat infant voluntarily according to the voluntary intention, but it was necessary to supply the test solution etc. as needed, and to control the experiment periodically and quantitatively in a more controlled manner. It is difficult to provide a test solution or the like.
3) As an artificial nipple for small animals such as mice and rats, the structure of the nipple of this device is too complicated, and the performance difference between nipples is likely to occur, so that the feeding amount and the like are difficult to stabilize.

Prior Art The complicated structure of the artificial nipple is devised to prevent leakage of liquid feed from the nipple as described above. However, for more stable feeding and more reliable data, the nipple has a simple structure, is easy to duplicate, and has excellent performance, and a liquid supply for laboratory animals that is assembled to fit the nipple There was a need for a method and equipment for it.

Shizuoka Society for Experimental Animal Research, Vol. 27, No. 1, Separate Volume, p.2-p.9, 2000.

  Therefore, the present inventors have proposed spontaneous oral administration in a well-controlled manner in accordance with the purpose of research, even when targeting experimental animals, particularly very small experimental animals with closed eyes and ears such as mouse infants. By making an artificial nipple capable of supplying liquid feed and test liquid in a suitable manner and a baby bottle suitable for use in combination with the artificial nipple, the experimental animal can be fed liquid feed or We have developed a liquid supply system for laboratory animals that can supply test liquid periodically and quantitatively, and the development of its use. The technical issues required for the artificial nipple, device and method can be summarized in the following A to D.

A. Adjustment of output condition of liquid feed: Experimental animals range from very small individuals such as mouse infants to individuals such as ferrets and rabbits according to the purpose of the study. For this reason, it is necessary to precisely adjust the output state of the liquid feed or the like according to the size and the state of the experimental animal. For example, too much liquid food or the like enters the lungs and causes pneumonia, and if it is hard to discharge, it stops drinking immediately. Also, if it is necessary to change the components of the liquid feed, etc. depending on the purpose of the research, the viscosity of the feed, etc. may change. You need to be able to do it.

B. Prevention of air retention in the stomach and intestines: When targeting rodents such as mice and rats, which are most commonly used as laboratory animals, mice and rats are considered You can't burp. Therefore, if air enters when a mouse or rat sucks and drinks a liquid feed, there is a problem that the air accumulates in the stomach and intestine and almost causes death. In rodents, the incisors are permanently extended, so if the incisors are extended to some extent (around the age of 10 days), the incisors will hinder the gaps between the nipple and lips, and air will be lost when feeding or administering the test solution. It is easy to smoke at the same time. Therefore, an artificial nipple that can cope with these problems is required.

C. Ascertaining the supply of liquid feed, etc .: For research purposes, it is necessary to accurately determine the supply of liquid feed, etc. Then, it is necessary to grasp the supply amount for each experimental animal, and it is necessary to easily grasp the supply amount during the feeding operation.

D. Artificial nipple has a simpler structure: The structure of the artificial nipple is easy to apply to very small nipples, and it is simple from the viewpoint of data comparison so that variations in individual nipples can be minimized. There is a need for a structure that provides good and good performance.

Regarding A, first, the structure was such that a replaceable thin tube was placed inside the artificial nipple, and by replacing it with a thin tube having a different inner diameter according to the required flow rate, it became possible to control the flow rate of liquid feed and the like. When it is necessary to control the flow rate more finely, a scaled tube is attached to the baby bottle so that the flow rate can be finely adjusted by the height (head) of the liquid feed or the like put in the tube.

Second, the inside of the nipple is filled with silicone rubber, isoprene rubber, styrene-isoprene rubber or the like or a sponge-like resilient member or formed integrally with the outer wall of the nipple, so that the liquid feeding material etc. The structure is such that it does not accumulate in the nipple other than the nipple and the thin tube. In this case, when formed integrally with the nipple outer wall, a cavity may be provided inside without filling the elastic member. These structures are intended to prevent the nipple from being crushed when the infant holds the nipple or sucks, so that a large amount of liquid feed or the like does not come out at once. This eliminates the need for the nipple to have a double structure, and simplifies the structure of the nipple, thereby achieving the task of D.

Furthermore, in order to prevent leakage of the liquid and control the flow rate more reliably, a mechanism was provided for controlling the internal pressure of the baby bottle used in combination with the artificial nipple to control the internal pressure and control the internal pressure. Specifically, a tube for adjusting the liquid volume, which was smaller by 20% or 30% than the expected amount of liquid to be swallowed at one time, was attached to the baby bottle. The tube for adjusting the liquid amount is crushed almost without resistance when sucking and sucking the infant, and does not affect the sucking operation of the infant. When the liquid volume adjustment tube is crushed, the supply of liquid stops, but in this state, the liquid volume adjustment tube can be expanded by applying pressure to the pressurization tube further provided outside the baby bottle with fingers or the like. Thus, it is possible to further drink the liquid of the inflated volume.

When the baby stops drinking and the pressurization with his / her fingers is stopped, the inside of the baby bottle becomes a negative pressure, and the liquid volume adjusting tube can stop the flow of the crushed liquid again. Thus, it is possible to simultaneously supply the liquid corresponding to the sucking amount of each baby and prevent leakage of the liquid.

It is also possible to use a pressurizing tube to prompt the baby to start drinking and drinking. That is, the baby feels that milk etc. has entered the mouth, not the time when the nipple enters the mouth, and starts sucking and drinking, so applying a slight pressure to the pressurizing tube and putting out a small amount of milk etc. from the nipple The time until the baby starts drinking and drinking can be shortened.

With the above configuration, the liquid feed or the like is supplied from the feeding bottle through the tubule to the mouth of the experimental animal directly from the artificial nipple in a controlled flow rate. That is, the flow rate of the liquid feed is firstly controlled by the inner diameter of the thin tube. Then, by adding a structure in which liquid does not accumulate in the nipple, irregular liquid leakage due to the sucking operation of the experimental animal is reduced. Further, by adding a mechanism in which the inside of the baby bottle becomes a negative pressure in accordance with the intake and drinking by using the baby bottle as a closed system, the supply amount of the liquid can be more finely controlled and the leakage of the liquid can be reliably prevented.

When a check valve is provided in a baby bottle according to the present invention, such a structure is not required on the side of the artificial nipple, so that the structure of the artificial nipple is simplified, and its manufacture, replacement, washing, etc. are facilitated. . However, even if a check valve is attached to the artificial nipple side, no problem occurs in the practice of the present invention. In this case, the non-return valve on the baby bottle side is unnecessary, but in view of the problem of D, the production surface of the artificial nipple, in view of the production cost, an embodiment in which the non-return valve is on the baby bottle side is a more preferable embodiment. It can be said.

B It is important how the nipple fits the mouth of infants to prevent the accumulation of air in the stomach and intestines. When an artificial nipple is used, it has been confirmed that the baby creates negative pressure with the tongue and hard palate and swallows liquid food. However, for example, in rodents, it has been found that when the baby is about 10 days old, the incisors are elongated, which hinders the swallowing of air. So by making the nipple larger as the baby grows so that the incisors do not get in the way, it is easier to create negative pressure with the tongue and hard palate (lip) as if a person sucks liquid with a straw, and the air can enter. Prevented. If the experimental animal is not a rodent (eg, a ferret), the shape of the nipple as well as the shape of the nipple may need to be changed to match the shape of the animal's mouth. However, in such a case as well, it is important to have a structure in which no liquid is stored in the nipple, and such a simple structure can flexibly cope with a change in the shape of the nipple.

C Grasp of the intake of liquid feed was achieved by installing a graduated cylinder in the baby bottle. In addition to the scale, the cylinder has a movable mark. This movable mark can be used for grasping the amount of intake by moving the mark in line with the liquid line when a plurality of babies continuously ingest liquid feed, or when injecting liquid into a baby bottle. It can be used to indicate the maximum liquid volume line. Further, this tube has a structure in which the tube itself can be replaced so that the tube diameter can be selected according to the size of the experimental animal. In addition to such a structure, a spacer for tube replacement was separately prepared.

As described in DA, the nipple portion is filled with an elastic member or formed integrally with an elastic member, and the structure that liquid does not accumulate in the nipple portion other than the nipple and the thin tube portion is This has not only simplified the structure of the artificial nipple, but has also been effective in the problem of preventing leakage of liquid when an experimental animal bites the nipple.

By the above solution, the present inventors are able to suitably combine an artificial nipple with an artificial nipple which is preferably used when a liquid feed or the like is spontaneously orally given to an infant such as a mouse or a rat. It has become possible to establish and provide a baby bottle designed to be used, and a liquid supply device and a liquid supply method for laboratory animals comprising the artificial nipple and the baby bottle described above.

  Hereinafter, a preferred embodiment of the present invention will be described in more detail with reference to FIGS.

FIG. 1 shows an artificial nipple of the present invention. In the figure, reference numeral 01 denotes a main part of an artificial nipple, which is a nipple and nipple portion integrally formed of a silicone rubber outer wall and a silicone sponge or an elastic body thereof, and 02 and 02 'indicate joints with a baby bottle.

The nipple of 03 is provided with a notch or 06 'hole indicated by 06, so that the liquid is supplied in accordance with the suction operation of the animal. In the case of a notch of 06, the same effect as changing the hole diameter depending on the strength of the suction operation of the animal can be used more suitably for the artificial nipple of the present invention.

The thin tube indicated by 07 is fitted with a tube having a different inner diameter as appropriate in consideration of the target experimental animal, its age, viscosity of the liquid feed, and the like. For example, the diameter of the injection needle is 25G-27G or the like, and the output condition of the liquid feed or the like can be adjusted accordingly. The length of the thin tube varies depending on the size of the nipple, but is, for example, 10 mm to 14 mm.

The material of the thin tube may be a member capable of maintaining the inner diameter, and may be appropriately selected from a hard tubular member used for liquid feeding, and a stainless steel tube usually used as an injection needle is suitably used.

Since the diameter of the tubule can be changed in this manner, liquid feeds applicable to the present invention include water, various aqueous solutions, low-viscosity compositions such as infusion compositions, milk for laboratory animals, enteral nutrition. An agent having a high viscosity such as an agent can be appropriately used.

When a silicon outer wall is used for the nipple part of 05, the thickness of the outer wall should be about 0.1 to 0.4 mm. Except for the nipple, the inside is filled with an elastic member such as a silicone sponge like 04. In this way, filling the nipple other than the nipple and the tubule with a resilient member, etc., to prevent the liquid from accumulating is because the experimental animal is liable to have liquid feed when it accumulates on the nipple. This is because when the nipple is bitten, the nipple is crushed and a large amount of liquid comes out at a time, which is a problem. In addition, having a structure in which liquid does not accumulate also has an advantage of preventing leakage of liquid. The elastic member used at this time may be any material that does not have hygroscopicity per se and can be generally applied to food containers and the like, and a sponge-like structure made of a material other than silicon increases elasticity. A material that can be provided, a high molecular rubber, or the like can be used.

When the artificial nipple is used more than once, the outer wall and the filler are preferably made of a material that can be used even after heat sterilization, for example, isoprene, silicon, a rubber such as a styrene-butadiene copolymer or a sponge-like material thereof. Can be selected. Above all, foamed silicon is easy to adjust elasticity appropriately and can be suitably used as a filler. Further, when the artificial nipple is not used a plurality of times, latex rubber also has an excellent point as a material used for the nipple portion, such as good absorption of animals.

It is necessary to arrange a check valve in order to prevent the liquid feed or the like from flowing back. When the check valve is attached to the artificial nipple side, as shown in FIG. 111, it is arranged together with a substrate such as 12 silicone rubber at the joint with the baby bottle. As the material of the check valve, it is preferable to use a material having the same hardness as the elastic member used for the nipple, such as silicone, elastomer, polypropylene, or a mixture thereof, or having an appropriate hardness.

In addition, reference numeral 08 denotes a support portion of a thin tube formed of silicon rubber or the like, and a member corresponding to the diameter of the thin tube of 07 is used. Reference numeral 09 denotes a base of the nipple portion having a flange shape, and has a function of fixing the artificial nipple when joined to a baby bottle. Reference numeral 10 denotes a play portion provided to cope with a case where the diameter of the thin tube of 07 fluctuates.

The four artificial nipples for mice and rats shown in Fig. 4 have different nipple sizes, small, medium, large, and large, depending on the age and size of the experimental animal. They are selected appropriately and used. That is, by always attaching an artificial nipple adapted to the size of the mouth of the experimental animal to the feeding bottle, it is possible to prevent the inhalation of air during feeding and the like. It should be noted that the numerical values shown in FIG. 4 are only reference values and are not limited to these numerical values.

As described above, according to the present invention, it is possible to prepare an artificial nipple according to the size of the animal and, in some cases, the shape of the mouth of the animal. This is one of the features of the method of the present invention. Therefore, in the present invention, not only mice, guinea pigs, rats, etc., but also comparatively large experimental animals such as rabbits and experimental animals having different mouth shapes from rodents such as ferrets of the weasel family are also intended as experimental animals. be able to.

The baby bottle part of the present invention has a check valve as shown in FIG. When this baby bottle is combined with the artificial nipple of FIG. 1 having no check valve, the product of the present invention can have more excellent characteristics. That is, the structure of the artificial nipple can be simplified, and the manufacture of the artificial nipple itself becomes easy. Along with that, it is easier to prepare nipples of different sizes, and it is more suitable for the purpose of the present invention that changes in nursing conditions suitable for various purposes can be realized simply by replacing with artificial nipples that meet the conditions. It becomes. Furthermore, there is an advantage that washing and regeneration of the artificial nipple is facilitated. However, in the case where the artificial nipple itself has a relatively large size, such as when there is no particular problem in its manufacture and handling, as described above, the present invention can be applied to the configuration in which the check valve is provided on the artificial nipple side as shown in FIG. There is no problem in the implementation of.

Further, the product of the present invention has the following excellent features by having a replaceable cylindrical structure in the baby bottle as shown in FIG.

That is, since the tube can be exchanged, even if the size of the animal changes from a mouse to a rat, by exchanging the tube via the spacer 21, a common baby bottle body can be used for the mouse and the rat. If spacers of several diameters are prepared, cylinders of various diameters can be joined to a baby bottle having one outer wall 19.

Furthermore, when the cylinder is graduated, the amount of the experimental feed or the liquid animal actually taken or administered can be easily measured one by one. At this time, as shown at 16 in FIG. 2, in addition to marking the scale line on the cylinder itself, a movable mark made of silicon rubber, various resins, etc. is attached so that the feeding amount of each baby can be adjusted. By moving the movable mark accordingly, the intake of the liquid feed can be measured more accurately. This movable mark may be formed in a ring shape, for example, and the required number may be fitted in a cylinder and used.

The material of the above-mentioned cylinder may be a member having transparency enough to confirm the contents and hardness enough to measure, for example, glass, polypropylene, polycarbonate, methylpentene resin which is a member usually used for an injection cylinder Alternatively, silicon rubber or the like can be used.

If the inner diameter d of the portion of the cylinder that is joined to the baby bottle on the cylinder side has a diameter that matches the insertion port of the baby bottle, the cylinder can be easily replaced. In this case, the spacer 21 becomes unnecessary. d is set so that the amount of liquid can be easily checked or in accordance with the amount of food or the like consumed by the animal. As an example, in the case of a mouse, it is preferable to use a cylinder having d of about 3 mm.

Also, the artificial nipple joint base shown in FIG. 2 and the capillary support 20 of FIG. 2 are formed of silicon rubber or the like, and have a removable structure. Therefore, not only washing and repair of the baby bottle, but also changing the size and material of each part according to the experimental animal can be easily performed.

In addition, reference numeral 18 denotes a tube which serves both for bleeding air and for cleaning the baby bottle, and reference numeral 17 denotes a tube for introducing a liquid feed or the like. The material of these tubes can be the same as that of the above tube. Reference numeral 22 denotes a joining tube for facilitating attachment and detachment of a tube or the like, and a stainless tube or the like is used.

The length of each part of the baby bottle main body shown in FIG. 213 may be appropriately changed according to the usage and purpose. For example, the length of L in FIG. 2 is about 100 mm in the case of a mouse infant, but it may be designed to be larger when the ability of the animal to drink milk or the like is high.

Further, the baby bottle part of the present invention has a flow rate fine adjustment mechanism shown in FIG. 3 as one of the embodiments. The flow rate fine-adjustment mechanism attaches a liquid volume adjusting tube and a pressurizing tube whose volume is smaller than the expected amount of liquid that the baby drinks at one time to the baby bottle of FIG. By adjusting the internal pressure with the above two tubes, the supply of liquid in accordance with the amount of sucking and sucking of the baby, the prevention of leakage of the liquid, and the promotion of the start of sucking and drinking were realized.

In other words, when feeding infants with milk at the stage where the infant has an artificial nipple in the mouth, first apply light pressure to the tube for pressurization with fingers, etc. Behavior is promoted and drinking is started immediately. By this mechanism, the waiting time until the baby starts spontaneously drinking and drinking can be greatly reduced. As drinking and drinking progresses, the inside of the baby bottle becomes negative pressure. At this time, the liquid amount adjusting tube changes from the state A shown in FIG. 3 to the state B, and the supply of milk or the like is stopped. At this point, if the baby further takes a sucking action, the user can press the pressurizing tube with his / her finger to bring the liquid volume adjusting tube into the state C, so that the sucking can be performed again. The liquid amount adjusting tube is brought into the state B again by drinking again, and the supply of the liquid is stopped. With this mechanism, it is possible to finely cope with the difference in the amount of drinking and drinking of each baby, and it is possible to more reliably prevent the leakage of the liquid. When feeding to another baby continuously, the feeding bottle may be once opened and the liquid amount adjusting tube may be returned to the state A.

In order to realize the above, the thickness of the liquid amount adjusting tube is set so that the tube is crushed without resistance so as not to affect the sucking and sucking of the baby. When the material is silicon rubber, the thickness is, for example, about 0.05 mm, and this thickness is selected as the bareest thickness that can maintain the shape. On the other hand, the pressure tube and the connection tube may be set to a thickness such that the tube is not crushed by the negative pressure when the baby drinks milk or the like. In the case of silicon rubber, the thickness is, for example, about 0.5 mm.

The material of the tube for pressurization and connection is not limited as long as it can realize the above function and can withstand heat sterilization treatment.For example, isoprene rubber, polypropylene, etc. can be used, but the required thickness differs depending on the material. There must be. The joining of these tubes is preferably performed via a heat-sterilizable stainless steel tube or the like in consideration of tube replacement and the like. If a spacer is used as in the case of the graduated cylinder, tubes of various diameters can be easily exchanged.

With the above-mentioned excellent characteristics, it is possible to spontaneously orally feed liquid feeds and the like to experimental animals such as mice and rats in the suckling period corresponding to premature infants in humans, Further, a liquid supply device for laboratory animals which can supply a liquid periodically and quantitatively by hand has never been realized, and is realized for the first time by the present invention. As described above, the artificial nipple of the present invention, a baby bottle suitable for using the artificial nipple, a liquid supply device for an experimental animal composed of an artificial nipple and a baby bottle, and the artificial nipple in the above-described device according to the state of the experimental animal. The method of exchanging laboratory animal fluids has many excellent features.

Hereinafter, the effectiveness of the present invention will be described based on test examples, but the present invention is not limited to these test examples.

(Test Example 1) Artificial rearing of mice using artificial nipples and feeding bottles for mice; Method for realizing growth by spontaneous feeding of infants; Artificial nursing was started using the small nipple and baby bottle of the invention for mice. The nursing cage for artificial nursing was kept warm on a commercial hot carpet. A bamboo basket was placed in the heat retaining cage, a chip was laid therein, and a pup mouse was placed. The chips outside the bamboo basket were watered occasionally to keep them moist. Before the start of artificial lactation, the offspring mice were separated from the parents for 3-4 hours. The artificial milk was prepared by dissolving 3.8 g of commercially available dog milk in 10 ml of hot water. After the milk was introduced into a baby bottle in which an artificial nipple was set by a pump, the baby bottle was inserted into a copper tube being kept warm while refluxing warm water, and heated for about 3-5 minutes. Heating was always performed before feeding each baby and as needed. Milk was fed 5-6 times between about 8am and 10pm, and 4-5 times after the 10th day. The amount of milk intake was determined by measuring the amount of milk reduced in the cylinder in the baby bottle (length of the cylinder: cm) before and after feeding, and weighing the pup before and after feeding. Breastfeeding was not performed for the artificially fed infants from around 10 o'clock at night to around 8 o'clock the next morning. Infants that started artificial lactation were kept in groups and were never returned to maternal nursing. Urination and defecation were performed by gently compressing the upper abdomen and back of the bladder several times a day as needed. Infants in the breastfeeding group were housed as usual in the same normal cage as the mother.
Experimental results: The results are shown in FIG.
Although the artificial infant was inferior in the growth rate to the mother's infant, as a result of using the product of the present invention, it was confirmed that the infant continued to ingest the artificial milk spontaneously at the time of feeding and grew without dropping out.

(Test Example 2) A certain amount of a test solution was orally administered using the product of the present invention instead of the gastric probe, and the effect of the test solution administration according to the method of the present invention on the growth of mouse infants was examined.
Test method: Three litters of BALB / C mice on day 12 of pregnancy were purchased from Japan SLC and spontaneously delivered in a stainless steel cage covered with a clean cap. Within 24 hours after birth, the pups are divided into two groups for each parent, combined so that the pups from each parent are evenly contained, and bred to two parents so that the total number of pups is eight each. Was. The test solutions used in the experiment are as follows. That is, a 0.5% -fructooligosaccharide-0.2M-sucrose aqueous solution was used as a test solution. The test solution was filled into the baby bottle for mice of the present invention using a disposable syringe to which a sterile tapered tip was connected, and was kept in a 50 ° C. incubator for 4 minutes. The mouse infants were separated from the parents on the first and second days after birth, and kept in a plastic cage floating in a 43 ° C. water tank for 2 hours. When the test solution was allowed to be fed to a mouse infant using a small-sized artificial nipple for a mouse of the present invention at a scale of a baby bottle for a mouse of 0.7 mm (about 50 μl), the nipple was immediately released from the mouth. Thereafter, the same amount of 0.2M-sucrose aqueous solution was drunk. By doing so, the amount of the drinking test solution could be accurately determined. The control group received a 0.2M-sucrose aqueous solution in the same manner. After administration of the test solution, the mouse infant was immediately returned to the cage of the mother animal (foster parent).
Experimental Results The growth curve of the infant is shown in FIG. The mouse infant to which the test solution was orally administered using the product of the present invention grew smoothly.
The product of the present invention can be used in experimental systems such as mice and rat babies, which are difficult to carry out gastric sonde method or catheterization as an experimental system to examine the effects of orally administering drugs and the like. It was confirmed that it was used effectively.

As described above, from the results of the test examples and the like, the artificial nipple of the present invention, a baby bottle suitable for use with the artificial nipple, a liquid supply device for an experimental animal including an artificial nipple and a baby bottle, and an artificial nipple in the above-described apparatus were used as an experimental animal. The experimental animal feeds spontaneously in liquid form by means of a liquid supply method for laboratory animals that is changed according to the condition of the animal. Thus, artificial lactation is possible without relying on breastfeeding of mouse infants and the like corresponding to unmature infants. In addition, the present invention makes it possible to orally and spontaneously administer various test solutions to infants such as mice and rats. It is possible to evaluate the effect of various test solutions by oral administration in a natural form on lactating animals that could not be obtained even though they were high. It has become possible to develop drugs and foods for premature babies and infants.

BRIEF DESCRIPTION OF THE DRAWINGS Sectional drawing which shows the artificial nipple of this invention. FIG. 2 is a partial cross-sectional view showing the baby bottle of the present invention. Sectional drawing which showed the mechanism which controls the internal pressure of a baby bottle. The figure which shows the example which changes an artificial nipple according to the size of an experimental animal. FIG. 3 is a result diagram of a test example in which a mouse infant was artificially nursed using the product of the present invention. FIG. 4 is a diagram showing the results of a test example in which a test solution was spontaneously orally administered to a mouse infant.

Explanation of reference numerals

04 Nipple portion to prevent liquid from accumulating 07 Replaceable thin tube portion 11, 14 Check valve 13 Baby bottle body 16 Replaceable tubular portion

Claims (10)

An artificial nipple for a laboratory animal, wherein the nipple has an exchangeable thin tube portion and a structure in which liquid does not accumulate in a nipple portion other than the nipple and the thin tube portion. 2. The artificial nipple for a laboratory animal according to claim 1, wherein the structure in which the liquid does not accumulate is formed by filling the nipple portion with an elastic member or by forming the elastic member integrally with the outer wall of the nipple. . The artificial nipple for a laboratory animal according to claim 1 or 2, wherein the artificial nipple has a check valve at a joint portion with the baby bottle. A baby bottle for use with the artificial nipple according to any one of claims 1 to 3, wherein the baby bottle has a replaceable cylindrical portion. The baby bottle for laboratory animals according to claim 4, wherein a scale for measurement and / or a movable mark is attached to the cylindrical portion. The baby bottle for laboratory animals according to claim 4 or 5, further comprising a check valve. 7. The baby bottle for a laboratory animal according to claim 4, which has a mechanism in which the internal pressure in the baby bottle becomes negative pressure when the laboratory animal drinks a predetermined amount or an arbitrary amount of the liquid to stop the flow of the liquid. When the experimental animal drinks a predetermined amount or an arbitrary amount of liquid, the internal pressure in the baby bottle becomes negative pressure and the flow of the liquid stops, and at that point, the experimental animal spontaneously releases the liquid by applying pressure from outside the baby bottle 8. The baby bottle for laboratory animals according to claim 7, which has a mechanism capable of being drunk. An experiment characterized by using any one of the artificial nipples selected from the artificial nipples according to claims 1 to 3 attached to any one of the baby bottles selected from the baby bottles according to claims 5 to 8. Animal liquid supply device. The method according to claim 9, wherein the size and / or shape of the artificial nipple is changed according to the size and type of the experimental animal.

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