JP2793776B2 - Enema - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel hygiene enema which prevents a decrease in the concentration of a preservative in an enema fluid in the enema.

[0002]

[Prior Art] EnemaDexterousContainers should be used to improve hygiene and nursing
Glass syringe type to reduce
Disposable general-purpose resin figsToStrange
The enema was sealed in this general-purpose resin containerEnemaBut
WideIt is in circulation. As a general-purpose resin used for this
Means polyethylene, polypropylene, polyvinyl chloride
And others. Among them, containers made of vinyl chloride resin
Discharges the enemaWhenThe deformation pressing force is low and it is restored
Due to its good responsiveness, it is excellent in operability and feel. Also
Vinyl chloride resin has good blow moldability and low cost.
In terms of points, it is also a leader among general-purpose resins. Only
And an enema using a conventional vinyl chloride resin containerIn a bowl
Indicates that the preservative concentration in the enema drops off during storage,
About 1.5 months after encapsulation, bacteria and mold will remain in the enema.
If you use it incorrectly, it will go from the anus to the rectum.
Problem of causing inflammation due to
No. Also, the cause of the decrease in the preservative concentration was unknown.

[0003]

[SUMMARY OF THE INVENTION The present invention, operability and excellent hand touch with a conventional vinyl resin vessel chloride, molding
While retaining the sex, preservative concentration in the enema liquid is reduced
Overcame the disadvantage of a withstand use Kunar, an object of Hisage <br/> supply of enema.

[0004]

SUMMARY OF THE INVENTION The present invention relates to a vinyl chloride system.
Results in a decrease of the preservative concentration enema using resin container stacked intensive studies with the aim of maintaining a constant range by kneading a predetermined amount of preservative in the vinyl chloride resin, the purpose is achieved is been completed by finding Rukoto, 100 parts by weight of vinyl chloride resin, a plasticizer 10 to 150 parts by weight and <br/> consisting preservative F parts by weight calculated from the bottom following formula 1 made of vinyl chloride resin In the container, enema with preservative concentration 0.015 ~ 0.06w / v%
The present invention relates to an enema, wherein a liquid is sealed. F = CbE / (100 d - Cb) ............ formula 1 [where, b is the time of the 1 the distribution ratio of the enema liquid preservative at coexistence of enemas and plasticizers and preservatives, distribution ratio to plasticizers preservatives, C is at <br/> necessary preservative concentration be maintained at enema solution (w / v%), a preservative in an enema solution 100ml
Expressed in weight g, E is added parts by weight of a plasticizer, d is Cb /
100 M (mol / ml) density of the plasticizer solution preservatives containing represented by (g / ml), M each table a molecular weight of preservative
You. ]

Hereinafter, the present invention will be described in detail. As the preservative used in the present invention, the same preservative used in the enema solution is added to the vinyl chloride resin. It is important to use those preservatives that are highly safe for the human body as much as possible. That is, benzoic acid, sorbic acid and its salts,
p- hydroxybenzoic acid esters, dehydroacetic acid, propionic acid and its salts, diphenyl, o- phenylphenol, have good to use those authorized as a food additive compendia such as thiabendazole. These salts and esters include sodium benzoate, potassium sorbate, p-
Isobutyl hydroxybenzoate, isopropyl p -hydroxybenzoate, p-hydroxybenzoic acid, ethyl p-hydroxybenzoate, butyl p-hydroxybenzoate,
Examples are propyl p-hydroxybenzoate, sodium dehydroacetate, calcium propionate, sodium propionate, sodium orthophenylphenolate . Other examples include naphthenic acid, β-naphthol, and p-nitrophenol, which are defined by the standard for cosmetic raw materials and the Japanese Pharmacopoeia Law.

The concentration unit used in the present invention will now be described. The preservative concentration C ( w / v% ) in the enema solution is (weight of preservative g
/ Enema liquid volume 100 ml), molar concentration mol / ml (mol number of solute / solution volume 1 ml), weight concentration w /
w% indicates the value of each in brackets as (solute weight g / solution weight 100 g).

As the enema, a solution obtained by dissolving a preservative in a mixture of glycerin and water is generally used, and an appropriate drug or nutrient is added for nutritional supplementation. The preservatives used in these enema solutions are preferably used alone or in combination of two or more, and the total concentration is preferably adjusted to 0.015 to 0.06 w / v%. 0.015w / v there is no preservative effect in less than%,
0.06 w / v% ultra Ell and individual differences easily irritate the mucous membranes and skin of some. In particular, have preferred that to 0.04w / v% from 0.02w / v%. In order for a user to have a distribution inventory and a use guarantee period of more than six months, it is necessary to maintain the concentration in this range for one year or more.

[0008] The present inventors have found that reduced by penetrating the plasticizer preservative in enemas is included in the vinyl resin container chloride. To maintain the required preservative concentration inventors also enema solution, when allowed to coexist aqueous glycerol solution and a plasticizer, a preservative in an aqueous glycerol solution is how dissolved is distributed plasticizer glycerin aqueous solution The distribution ratio is measured, and the preservative concentration to be maintained and stabilized in the enema solution is multiplied by the distribution ratio b to determine the amount of the preservative to be kneaded into the vinyl chloride resin . It was heading.

The method for obtaining the distribution ratio will be described with reference to two examples. First, a first example will be described. An arbitrary amount of a preservative is dissolved in an aqueous glycerin solution and / or a plasticizer, and the two solutions are placed in a separatory funnel and shaken vigorously for 60 minutes or more, and then allowed to stand until they separate into two layers. This is desirably left for at least three days. The concentration of the preservative dissolved in each separated layer was quantified, and the molar concentration (mo
l / ml) ratio or weight / volume concentration (w / v%) ratio is defined as the distribution ratio. The quantification of the preservative is performed by a known GCP analysis. Beforehand, a calibration curve of absorbance-concentration is prepared based on the preservative passage time (retention time) of the preservative used and the maximum absorption wavelength of the preservative, and then the solution of each layer is subjected to liquid chromatography, and The preservative is identified and separated from the retention time by applying the wavelength light used for preparing the calibration curve, and the concentration is determined from the absorbance. This operation may be performed in a representative temperature 23 ° C. the enema is retained and used, in particular, measured at 10 ° C. increments for 50 ° C. from -10 ° C., preferably set to an average of 7 points.

[0010] In the first example was quantified preservative distribution ratio between aqueous glycerol solution and a plasticizer, it can also be quantified distribution ratio between the aqueous glycerol solution and vinyl chloride resin composition. This will be described as a second example. An arbitrary amount of preservative is dissolved or mixed in the glycerin aqueous solution and / or the vinyl chloride resin composition, and the vinyl chloride resin composition is formed into a sheet, and the sheet is added to the glycerin aqueous solution.
Except for soaking for 40 days or more, or forming a container for an enema with this vinyl chloride resin composition, injecting the glycerin aqueous solution into this and leaving it for 40 days or more to reach equilibrium,
Take the same method as in the first example. However, plasticizers and preservatives in the vinyl chloride-based resin composition is quantified by extraction with ether.

[0011] These both cases, rather than by if antiseptic concentration of the two-layer after the distribution is known, preservatives concentration for each layer prior to installation may even unknown. Conversely, for each layer before installing the two layers, know the preservative concentration, layer weight or / layer volume and density, and if the preservative is distributed in a closed system, using the law of conservation of mass, the preservative concentration measurement has good be carried out either one layer. Of these two examples , the first example is recommended because it can be measured in a short period of time and is simple, but the distribution ratio measurement method is based on the condition that a glycerin aqueous solution layer and a plasticizer layer that do not mix with each other coexist. What is necessary is just to measure the concentration of the preservative that can be dissolved in both of these layers and reach equilibrium in both layers, and the operation method is not limited to these two examples.

Using the thus obtained partition ratio of the preservative , that is, the ratio A / B of the preservative concentration (mol / ml) of the aqueous glycerin solution to the preservative concentration (mol / ml) of the plasticizer, the enema is obtained. The amount F (parts by weight) of the preservative kneaded into the vinyl chloride resin to maintain the preservative concentration in the liquid at C (w / v%) is determined by the above formula 1. At that time , it is necessary to measure the density d (g / ml) of the plasticizer solution containing the preservative of this concentration and substitute it into the equation (1).

Equation 1 will be described. A: distribution ratio of preservative to enema when coexisting with enema and plasticizer; B: distribution ratio of preservative to plasticizer when coexisting of enema and plasticizer, especially when A = 1 B is represented by b. The concentration of the preservative to be maintained in the enema is defined as C (w / v%), which is converted into a molar concentration to be C / 100 M (mol / ml) (M: molecular weight of the preservative) . Therefore, the preservative concentration X (mol / ml) in the plasticizer required to maintain the preservative at a concentration of C / 100 M (mol / ml) in the enema is Cb / 100 M. Concentration X (mol / m
measuring the preservative containing plasticizers density of the solution d of l) (g / ml), when obtaining the plasticizer weight of a preservative-containing plasticizer solution 1 in g of X (mol / ml), ( 1- XM / d) . XM /
d is a preservative amount of a plasticizer solution 1 in g preservative containing the remainder becomes a plasticizer (1-XM / d). X = Cb / 100
When M is substituted , 1-XM / d becomes 1-Cb / ( 100d ). This becomes a plasticizer weight g in plasticizer solution 1 g of a preservative containing a concentration X (mol / ml).

In order to produce a vinyl chloride resin container,
When it is desired to add E parts by weight of the plasticizer to 100 parts by weight of the vinyl chloride resin, the preservative addition amount F (parts by weight) required to maintain the essential preservative concentration in the enema is [ MCb /
(100 Md)] × [E / (1- Cb / 100 d)] = CbE / (100d
- represented by Cb) ... (Equation 1). Explaining this equation 1, XM / d = (Cb / 100M) M / d = MCb / 100Md
Next, [MCb / (100 Md) ] is X (mol / ml) of preservative
The unit is g / g in terms of the weight of preservative per g of the plasticizer solution containing g . [E / (1- Cb / 100 d)] a solution plasticizers preservatives containing the X (mol / ml) containing a plasticizer E g
Is what g is calculated, and the unit is g . Therefore, the preservative of X (mol / ml) is added by adding a preservative to the plasticizer Eg.
To the congestion of plasticizer solution, MCb / (100 Md) ×
It becomes - (Cb 100 d) g [ E / (1- Cb / 100 d)] requires preservative g, summary CbE /. If the plasticizer Eg is added to 100 g of the vinyl chloride resin, the plasticizer E
Parts by weight, can be converted to F parts by weight of preservative.

From the previous studies, the retention rate of the preservative in the enema solution of the vinyl chloride resin container to which the preservative F (parts by weight) determined by Formula 1 was added was 10 specimens described in the Examples. Μ ± 3σ when population average μ and population variance σ2 are (95.3 ± 2.
40)%. Preservatives are slightly reduced because the partition ratio measurement is measured before full equilibrium in accelerated tests,
It can be considered that the preservative is selectively evaporated and lost by heat during molding, that the preservative is slightly absorbed by the composition other than the plasticizer, and that the second example is problematic in terms of the extraction rate from the container. However, the cause has not been identified. However, the preservative initial concentration (preservative concentration to be maintained) C is
Considering the maintenance rate of (95.3 ± 2.40)%, seeing safety 0.015w
/ v% to 0.06w / v%, F
It is easy to stabilize the preservative concentration in the enema of the vinyl chloride resin container into which (parts by weight) preservative is kneaded, in the most preferable range of 0.02 w / v% to 0.04 w / v%. .

[0016] The preservative particular limitations on the method of kneading the vinyl chloride resin without preservatives F parts by weight as determined by the formula 1, plasticizer E parts by weight vinyl chloride resin 100 parts by weight of various described later A method of dispersing and dissolving a predetermined number of added components in a compounding machine such as a ribbon blender, a Henschel mixer, a high-speed mixer, or a single-screw or twin-screw extruder of this vinyl chloride resin composition, a Banbury mixer, a pressure kneader,
A method of uniformly kneading, dispersing and dissolving using a kneader such as a kneader or a roll may be used. In addition, no difference was observed in the effect of preventing the preservative from decreasing even if a step of dissolving the preservative in the plasticizer before and after the dispersing and dissolving was performed by the compounding machine. Dispersed and dissolved preservative containing vinyl chloride resin composition in this way, powder, block body, as a sheet or pellets, is sent to a molding step of the next enema dexterity container.

The vinyl chloride resin container used in the present invention is required to be as safe as medical plastics and food containers, and has been prepared by the US FDA standard and the PVC Food Sanitation Council. Voluntary Regulations on Containers and Packaging (PL Standard Revision 9th Edition) PVC Food Sanitation Council
1989.3 "(hereinafter abbreviated as PL standard) and" Medical Plastics Voluntary Standard "created by the Japan Medical Plastics Association.
(Hereinafter abbreviated as medical standard). Therefore, plasticizers and vinyl chloride resin as a base polymer that constitute the vinyl chloride resin container , polymer additives,
Stabilizers, antioxidants, ultraviolet absorbers, surfactants, lubricants, coloring agents, fillers, foaming agents, and other additives are FD
When using a product approved by the A standard or the PL standard, or using an unapproved chemical , make sure that the vinyl chloride resin container containing the material has a material test and a dissolution test (PL test) specified in Chapter 2 of the PL standard. Abbreviated as test) or medical vinyl chloride resin compounds I and II specified in medical standards
(Abbreviated as medical test). Examples of unapproved drugs include, for example, trimellitic acid esters, alkyl esters of pyromellitic acid, esters of dimethyl carbonate and polyhydric alcohols for plasticizers, and Ba-Zn based stabilizers for stabilizers. Known ones, including the composition, are mentioned.

The molding of the enema dexterity containers <br/> device from the vinyl chloride resin composition, direct blow, sheet blow is carried out by blow molding such as injection blow, the workability and, enemas operability and hand touch A combination of a plasticizer and a vinyl chloride-based resin which greatly affects any of the preservative reduction phenomena will be described. It is considered that the decrease of the preservative in the enema is due to the transfer of the preservative to the container, and particularly the preservative is absorbed by the plasticizer constituting the container. However, the plasticizer is indispensable for adjusting the touch feeling of the deformation pressing force of the container and improving the processability. These plasticizers may be used alone or in combination of two or more. When two or more kinds are used in combination, the distribution ratio is measured between a predetermined amount of the mixed plasticizer liquid layer / or a vinyl chloride resin composition kneaded with a predetermined amount of several kinds of plasticizer and the glycerin aqueous solution layer. The amount of the plasticizer is 10 to 150 parts by weight based on 100 parts by weight of the vinyl chloride resin. If the amount is less than 10 parts by weight, the plasticizing effect is not sufficiently exerted, the flowability is reduced, and the processability is deteriorated, and the molded product is hardened, and the enema operability and the feeling of touch are deteriorated. When the amount exceeds 150 parts by weight, drawdown is caused to deteriorate workability, and tackiness appears on the surface of the container, and mechanical properties tend to decrease.

In the present invention , a polymer used as a backbone polymer
The vinyl chloride resin is, for example, a vinyl chloride homopolymer, a post-chlorinated vinyl chloride polymer, a partially cross-linked vinyl chloride polymer, a copolymer of vinyl chloride and a polymerizable monomer other than vinyl chloride, and a graft of vinyl chloride. Selected from grafted copolymers and the like. These vinyl chloride resins are
They may be used alone or in combination of two or more,
The average degree of polymerization is desirably in the range of 300 to 10,000. If it is less than 300, sufficient strength and deformation responsiveness cannot be obtained, and the flowability is too high, resulting in poor processability, or drawdown to fail to obtain a container having a uniform thickness. If it exceeds 10,000, elasticity is exhibited at the time of processing and processing becomes difficult.

[0020] Plasticizers used in the present invention, diethyl phthalate, di -n- butyl, dihexyl phthalate, diheptyl phthalate, dioctyl phthalate (hereinafter D
OP) , phthalic acid esters such as didecyl phthalate and diisononyl phthalate; dioctyl adipate;
Adipic acid didecyl, diisobutyl adipate, diisononyl adipate, n- octyl, sebacate -n- butyl, dioctyl sebacate, aliphatic dibasic acid esters such as azelaic acid ester; phosphoric acid esters, tributyl citrate, Polyhydric carboxylic acid esters such as mono-, di-, tristearyl citrate and triethyl acetyl citrate; polyhydric alcohol esters such as glycerin; epoxy-based plasticizers such as epoxidized soybean oil and epoxidized castor oil; polyester-based plasticizer Agents and the like.

If emphasis is placed on the enema operability and hand feeling as described above , a plasticizer having a high plasticizing effect may be added as much as 150 parts by weight or a vinyl chloride resin having a high degree of polymerization may be selected. If the emphasis is on processability , a degree of polymerization of 3
It is preferable to select a vinyl chloride resin having a low degree of polymerization with a limit of 00 and adjust the plasticizer to an appropriate amount. Further, a conventional method of adding an acrylic polymer processing aid for preventing drawdown may be used. Vinyl resin container chloride used in the present invention is to establish the amount of the preservative in the method, said mixed and dissolved in a vinyl chloride resin wherein the method, processing the enema dexterity container blow molding of the Is done. An enema liquid according to the application is injected into the vinyl chloride resin container by a fixed-rate discharge pump such as a tube pump or a plunger pump, and the enema discharge port is subjected to heat welding, ultrasonic welding, high-frequency welding,
Sealed with such fastening fitting cap, enema is completed using a vinyl resin container chloride of the present invention.

[0022]

According to the present invention , it is possible to maintain the operability, excellent feel and feel, and moldability of a vinyl chloride resin container.
Et al., To prevent a decrease in preservative concentration enema solution can be provided at low cost an excellent enema safety and hygiene.

[0023]

EXAMPLES Next a more detailed description of the present invention through examples, but the present invention is not limited to these examples. (Example 1, Comparative Examples 1 to 3) Glycerin 50 w / w% as in Example 1, deionized water 50 w /
w% glycerin aqueous solution and 0.0282 w / v% p as preservative
-Ethyl hydroxybenzoate (hereinafter abbreviated as EpHB) and 0.01
The present invention will be specifically described by taking, as an example, a container made of a vinyl chloride resin into which an enema solution (hereinafter abbreviated as an enema solution) obtained by dissolving 12 w / v% butyl p-hydroxybenzoate (hereinafter abbreviated as BpHB) is used. explain. First, the distribution ratio of the preservative between the aqueous glycerin solution and the plasticizer is determined. The distribution ratio is determined by the method described later, and the amounts of EpHB and BpHB calculated by using Equation 1 are added to the vinyl chloride resin. and, molding the <br/> vinyl chloride resin container (hereinafter referred to as an appropriate amount container composition) is kneaded with a plasticizer, with this, 1 year, EphB enema solution
A storage test was performed to track concentrations and BpHB concentrations. As well
To, EphB as Comparative Example 1, (abbreviated as additive-free containers composition below) vinyl resin container chloride BpHB no addition, Comparative Example 2
As a container made of a vinyl chloride resin (hereinafter abbreviated as a container with an insufficient composition) in which the amount of EpHB and BpHB added is smaller than that of a container having an appropriate amount of composition. A storage test was performed on a container made of a resin (hereinafter abbreviated as a container with an excessive amount of composition). Each storage test was carried out in a box that was not particularly temperature-controlled.

The raw material composition of each container which is calculated by the above method
And the details of each component are shown in Table 1 (the numbers in the table are parts by weight) .
In the raw material composition of each container, the proportions of the components other than EpHB and BpHB were all common. All of these components are approved by the FDA or PL standards.

[Table 1]

First, the distribution ratio is measured. All measurement operations
Performed at 23 ° C. DOP 91.38 w / w% and epoxidized soybean oil 8.
The DOP solution consisting of 62w / w%, 4.8w the EphB / v% and BpHB
It was dissolved by adjusting the 13.76w / v% (hereinafter this DOP solution abbreviated as D1 solution). EpHB 0.0278w / v% and BpHB 0.011
A glycerin aqueous solution (hereinafter abbreviated as GH1 solution) containing 50% w / v% glycerin and 50% w / w pure water was prepared. Approximately 50 ml of the D1 solution and approximately 40 ml of the GH1 solution were poured into a 200 ml separatory funnel, sealed, and vigorously stirred for 60 minutes with an automatic shaker. When this was allowed to stand for 7 days, it was clearly separated into two layers visually. A high-density glycerin aqueous solution layer (hereinafter abbreviated as GH2 liquid layer) is provided as a lower layer, and a DOP solution layer (hereinafter referred to as D2
Liquid layer) became the upper layer. When the EpHB and BpHB concentrations in the D2 liquid layer and the GH2 liquid layer were measured by the following method, the concentrations were different from those of the initial D1 and GH1 liquids. In both EpHB and BpHB, the DOP solution layer was transferred to the glycerin aqueous solution layer.

(Method of Measuring EpHB and BpHB Concentrations) Quantification of EpHB and BpHB was performed by a known method. That is, 195
The measurement was performed by high performance liquid chromatography equipped with an absorbance integration function with an absorbance detector of nm to 350 nm. An eluent composed of about 30% w / w% aqueous methanol was flowed at a flow rate of 1.0 ml / min, and about 0.02% w / v% of methanol solution of EpHB was injected.The maximum absorption wavelength was 260 nm, and the retention time was 4.35 to 5.10 minutes. Observed. With the same operation, BpHB was observed with a maximum absorption wavelength of 260 nm and a retention time of 7.75 to 9.42 minutes, indicating that EpHB has a shorter retention time, and that even at the same wavelength of 260 nm, EpHB and BpHB can be distinguished and identified by the retention time. . The aqueous glycerin solution did not absorb at 260 nm, and the DOP solution had different retention times and did not affect the identification of EpHB and BpHB. The integrated value of 260 nm absorbance on the retention time axis is proportional to the EpHB and BpHB concentrations in the sample. Utilizing this, four known concentrations were prepared for 0 to 0.05 w / v%, and a calibration curve of the integrated absorbance value and the concentration was prepared. Subsequently, the absorbance integral value was measured for each sample, and the EpH
B, BpHB concentrations were read. If the absorbance integral was too high and outside the calibration curve, it was diluted with an aqueous methanol solution and placed on the calibration curve.

The EpHB and BpHB concentrations of the D2 liquid layer and the GH2 liquid layer were converted into molar concentration mol / ml, and the EpHB and BpB of the GH2 liquid layer were further converted.
Table 2 and Table 3 show the distribution ratio as a ratio when the HB concentration is set to 1.
It described in. EpHB is 0.1010w / v% in glycerin aqueous solution,
When the glycerin aqueous solution was set to 1 at 4.808 w / v% in the DOP solution, the distribution was 47.60-fold in the DOP solution. BpHB is 0.03197w / v% in glycerin aqueous solution and 14.72w / v in DOP solution.
In v%, when a 1 glycerin aqueous solution, the DOP solution
It was distributed 460.3 times. Both EpHB and BpHB were remarkably distributed in the DOP solution, and the distribution ratio of BpHB to the DOP solution was particularly high.

[Table 2]

[Table 3]

Next, the embodimentAnd eachThe enema of the comparative example
Use equation 1 to maintain the EpHB and BpHB concentrations.
The amount F (parts by weight) of the preservative to be added to the resin is calculated.
First, the addition amount of EpHB F_E Is calculated. EpHB molecular weightM _E 
=166.18, maintenance concentrationC _E =0.0282 w / v%, b_E = 47.57
AsC _E b_E =4.808w / v% EpHBofPlasticizer solutionToAnother
When the density was measured, D _E(g / ml)=0.
986. Plasticizer addition amount E = 58 parts by weight
From Equation 1,F _E =0.7999, 0.8 parts by weight
I decided that. Similarly BpHBofKneading amountF _B Is calculated.
M _B =194.23, maintenance concentrationC _B(w / v%)=0.0112, b_B =46
0.3, C _B b_B =14.72w / v% BpHBofPlasticizer solutiond
_B(g / ml)=0.986, plasticizer addition amount E = 58 parts by weight,
WhatF _B =3.199 and 3.2 parts by weight
Was. Thus, the composition was determined.

[0029] Using each set <br/> forming raw material composition and Comparative Examples 1 to 3 of Example 1 was injected enemas 120g in each container produced by a known method, sealing the mouth portion at a high frequency welding Stopped and a storage test was performed. The day when the enema was enclosed was defined as the starting day 0. Tables 4 and 5 show the results of the one-year storage test. Changes in the concentrations of EpHB and BpHB are shown in FIGS. 1 and 2, respectively, with the preservative amount of each enema solution on day 0 of the start as 100.

[Table 4]

[Table 5]

[0030] Using the appropriate amount containers of the composition of Example 1 enema
Only the vessel showed 100% EpHB and BpHB concentration maintenance characteristics.
In the non-added container having the composition of Comparative Example 1, the amount of the preservative was greatly reduced, and mold was observed on the 185th day. Enema with excess containers composition of Comparative Example 3 had exceeded the mucosal irritation permissible concentration on day 20. The amounts of EpHB and BpHB added in the composition are the saturated amounts of the DOP solution at 23 ° C. In this way it is not intended that not good if Kome Neri saturation amount could be confirmed. Comparative Example 2
Enema with shortage containers composition was slight mold was observed at day 363 days. Above embodiments, as shown in Comparative Examples, the addition of proper amounts of antiseptic agent in the vinyl chloride resin, by kneading, to provide a can prevent the occurrence of fungi, it is excellent in hygiene enema Can be.

Reference Examples 1 to 7 Reference Example 1 is a case where the container of Example 1 was used (Table 4).
And Table 5). In the enemas of Comparative Examples 2 and 3 , C = 100Fd / (E + F) b is derived from Equation 1, and EpHB, BpHB
The number of added parts E, the number of plasticizer parts F, the preservative and the plasticizer solution are prepared in this number, the density is d, and b _E = 47.57 and b _B = 460.3 obtained from the distribution ratio measurement test are substituted. Ru can be obtained a preservative enema solution should be maintained in the reverse concentration C (w / v%). The enemas of the preservative concentration C (w / v%) was prepared, Comparative Example 2, was filled in a container of Comparative Example 3 was allowed to stand for one year, one year preservative concentration C (w / v%) EpHB, Bp in enema after
In comparison consider the concentration of HB, can be confirmed certainty of formula 1
(This was referred to as Reference Examples 2 and 3) . Among other preservatives, the distribution ratio of isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate and propyl p-hydroxybenzoate was measured in the same manner as in Example 1, and the preservative to be maintained was used. defining a concentration C (w / v%), a <br/> enemas of this concentration were prepared and shelf test of 1 year as enema and filled into containers. This consider went also to 併 (this
Reference Examples 4 to 7) . Table 6 shows the results.

[Table 6]

For 10 samples, the preservative concentration H in the enema solution after one year was an average (95.3 ± 2.40)% of the target preservative concentration C (w / v%) to be maintained . showed that. As described above, the distribution ratio measured from the distribution test can be applied to various preservatives in a wide concentration range, and the preservative concentration in the enema solution after production can be reliably controlled by the preservative addition amount F calculated by the formula 1. It became so. As a result, the generation of mold can be prevented, and an enema having excellent hygiene can be provided.

[Brief description of the drawings]

1 is a graph showing changes in one year EpHB concentration enema solution.

2 is a graph showing changes in one year BpHB concentration enema solution.

Claims (2)

(57) [Claims] 1. 100 parts by weight of a vinyl chloride resin , a plasticizer 10 to
150 parts by weight, and preservatives F parts by weight calculated from the bottom following formula 1
Comprising vinyl chloride resin vessel, preservative concentration 0.015 ~
An enema characterized by encapsulation of 0.06 w / v% enema
Bowel. F = CbE / (100 d - Cb) ............ formula 1 [where, b is the time of the 1 the distribution ratio of the enema liquid preservative at coexistence of enemas and plasticizers and preservatives, distribution ratio to plasticizers preservatives, C is at <br/> necessary preservative concentration be maintained at enema solution (w / v%), a preservative in an enema solution 100ml
Expressed in parts by weight ( g) , E is a part by weight of a plasticizer, and d is Cb / (1
00 M) (mol / ml) density of the plasticizer solution preservatives containing represented by (g / ml), M represents respectively a molecular weight of preservative. ] 2. The method of claim 1, wherein the preservative is p-hydroxybenzoic acid ester.
The enema according to claim 1, which is: