JPH0446102A - Sustained release preparation - Google Patents

Abstract

PURPOSE:To obtain a sustained release preparation in which control of a packing amount is carried out without impairing performances by packing a volatile substance of perfume, pheromone, medicine, etc., into a tube made of a polymer material and pressing the packed tube. CONSTITUTION:A volatile substance is packed into a tube made of a polymer material (e.g. polyethylene or ethylene-vinyl acetate copolymer) having 0.5-5 mm average inner diameter and 0.1-3 mm thickness and the packed tube is pressed to control the packed amount to 95-10% of amount before pressing and then sealed to produce the aimed sustained release preparation. A method in which the volatile substance-packed tube is inserted into a pair of rolls controlled in the space and pressed is advantageous as the method for pressing, because the method can continuously be carried out. When the rolls are previously heated, crack of the tube is prevented. Excess packing is prevented and packing can be carried out in a minimum amount even when a substance having high viscosity is used.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention stores volatile substances such as fragrances, pheromones, medicines, and agricultural chemicals, and allows the contents to be dispensed in fixed amounts by leaving them in a predetermined place for a long period of time. This invention relates to a sustained-release preparation that can be continuously volatilized.

(Prior Art) Demand for sustained-release preparations that meet the above objectives has been increasing in recent years, and various proposals have been made in this regard.

As one such technique, US Pat. No. 3,539,465 and US Pat. No. 3,577,515 disclose formulations containing volatile substances in microcapsules.

This often results in the loss of volatile substances to be contained during microencapsulation, and it is difficult to maintain uniform sustained release over a period of one month or more.

On the other hand, U.S. Patent No. 4,017,030 discloses a preparation in which a volatile substance is stored in hollow fibers, but it has the drawbacks of high volatilization rate and inability to store a large amount of volatile substance. .

Patent No. 1 solves these drawbacks. ．． There are inventions of No. 350゜282 and No. 1,406,973,
These tubes are made of a polymeric material and are filled with a volatile substance and sealed at both ends so that they can contain a relatively large amount of volatile substance and can be released stably and slowly over a long period of time.

(Problem to be solved by the invention) However, even with these sustained-release preparations, in order to achieve more uniform sustained release to the target substance, depending on the volatile substance contained, it is necessary to adjust the filling amount without changing the outer surface area of the tube. It may be necessary to increase the treatment area or treatment density with the same amount of volatile material. At this time, if you try to make a tube with a uniform thickness by reducing the inner diameter, the filling amount and thickness tend to be uneven, which causes the release rate of volatile substances to fluctuate and deteriorates the performance as a sustained release drug. There is.

In addition, filling a tube made of a polymer material with a volatile substance is usually done by increasing or decreasing the pressure inside the tube, but if the volatile substance has a high viscosity, it takes a lot of time to fill it, and in addition, When reducing the inner diameter of the tube to reduce the amount of filling, there were cases in which filling could not be performed due to viscosity. Therefore, if the inner diameter of the tube is increased to make it easier to fill, the amount of filling becomes excessive and the cost increases.

Therefore, an object of the present invention is to provide a sustained-release preparation that allows easy filling of volatile substances and adjustment of the filling amount without impairing the performance of the sustained-release preparation.

(Means for Solving the Problems) As a result of intensive research to solve the above problems, the present inventors found that when a tube is filled with a volatile substance and then pressed, the performance as a sustained-release preparation is improved. without damaging
The present invention was completed by discovering that the filling amount of volatile substances can be easily adjusted.

In other words, whereas in conventional tubular sustained-release preparations, both ends of the tube were sealed after filling the tube with a volatile substance, in the sustained-release preparation according to the present invention, the tube is pressed before being sealed. The feature is that the filling amount of volatile substances is adjusted by crushing.

To explain this, this pressing method involves inserting a tube filled with a volatile substance between a pair of rolls with an adjusted gap and crushing it, which is industrially advantageous because it can be done continuously. However, it is not limited to this. Furthermore, it is preferable to preheat the rolls during this pressing because this will prevent cracking of the tube.

The degree of pressing is such that the filling amount after adjustment is 9% of the filling amount before pressing.
It is preferable to adjust the amount to 5 to 10%.

If this exceeds 95%, press the filling amount*
The purpose of the present invention cannot be achieved because the meaning of "a" is lost. Further, if it is less than 10%, the amount of volatile substance filled is reduced too much, the release period is shortened, and the release rate in the latter half of the release is also reduced, which is not preferable.

The tube thus pressed is sealed and cut into predetermined lengths for practical use.

The tube used in the present invention has an average inner diameter of 0.5 to 5I.
, one made of a polymeric material with a wall thickness of 0.1 to 3 mm is preferable.

Tubes with an inner diameter of less than 0.5 mm are industrially disadvantageous because filling with highly viscous volatile substances takes a lot of time and is difficult to form, and the amount of filling decreases when pressed. It becomes impossible to emit volatile substances stably for a long period of time. Moreover, tubes with an average inner diameter exceeding 5 mm are economically wasteful and impractical.

The thickness of the tube, along with the type of material, has a large effect on the rate of release of volatile substances, so what is required? ) It is desirable to choose a material with a thickness suitable for the speed, but those less than 0゜1 m1 are extremely difficult to mold, and those thicker than 3III reduce the rate of release of volatile substances and are not suitable for practical use. Not only this, but also cracks are likely to occur during pressing, which is undesirable.

The cross-sectional shape of the tube before pressing may be any shape such as circular, square, or star-shaped, but since fine irregularities on the tube surface are crushed by pressing, a simple shape such as circular or square is practical.

The overall shape of the tubular sustained-release preparation may be arbitrary, such as spiral or snail-shaped, or may have a metal wire attached to the tube to facilitate application to the treated body. You can choose.

The polymeric materials used to form the tube are those that are effective in controlling the rate of volatile material release, such as polyethylene, ethylene-vinyl acetate copolymer, ethylene-ethyl acrylate copolymer, polypropylene, poly- 4-methylpentene-1, polyvinyl chloride, polyvinylidene chloride, fluorinated polyolefin, cellulose acetate,
Examples include acrylic esters, and if necessary, plasticizers, lubricants, antioxidants, stabilizers, colorants such as dyes or pigments, ultraviolet absorbers, and the like may be used in combination.

Examples of volatile substances include sex pheromone substances, volatile agricultural chemicals such as diazinon and dimethyldichlorovinyl phosphate, fragrances, and various physiologically active substances.

(Examples) Hereinafter, specific aspects of the present invention will be explained using Examples and Comparative Examples, but the present invention is not limited to these Examples.

Example 1 One end of a high-density polyethylene tube with an average inner diameter of 0.61°, a wall thickness of 0.3cm, and a length of 500 m is depressurized, and the other end is 3K
By applying a pressure of g/dG, a 1=1 mixture of 11-hexadecenal and 11-hexadecenyl acetate, which are sex pheromone for the diamondback moth, was filled into the tube over a period of 4 hours. this? While pressing with J pairs of rolls with a diameter of 15011 adjusted to a clearance of 0.8 m at 70°C, sealing was performed by high frequency heating every 20 a++ to obtain a rope-shaped sustained release preparation.

The amount of pheromone loaded per 201 of this preparation was 39 ■, which was 65% of the amount loaded before adjustment.

A length of 77 m of the obtained rope-shaped sustained release preparation was used and cut at the sealed portion to make the length match the shape of the field.

They were spread out at 6m intervals over a cabbage field with a total area of 5a.

As a result, the density of diamondback moth larvae decreased, and the communication disruption rate was 99% on average, with a minimum of 95%, indicating a stable communication disruption effect.

Comparative example 1゜The sex pheromone of the diamondback moth was prepared in the same manner as in Example 1, and the length was 50 mm.
After filling a 0m high-density polyethylene tube, 20
Each a++ was sealed by high frequency heating to form a rope-shaped sustained release preparation. The amount of pheromone loaded per 201 of this preparation was 60 .

The total amount of sex pheromone used is as shown in Example 1. In order to achieve the same result, a rope-like preparation with a length of 50 m was cut to an appropriate length and stretched around a cabbage field with a total area of 5 a at intervals of 9 m.

As a result, the communication disturbance rate was confirmed to be effective with an average of 98%, but depending on the day, diamondback moths were also observed to be attracted and killed by the attraction traps set in dry quantities, and the communication disturbance rate was at least 87% on some days. The stability of the communication disruption effect was inferior to that of Example 1.

Example 2 8,10-dodecagenyl alcohol, which is a sex pheromone of the codling moth, was mixed into an ethylene-vinyl acetate copolymer with an inner diameter of 1.0 m+o and a vinyl acetate content of 6%.
A tube with a wall thickness of 0.3 mm was filled in the same manner as in Example 1. While pressing this tube with a pair of rolls with a diameter of 153 adjusted to a clearance of 0.95aIa at 50°C, the tube was sealed by high-frequency heating every 20 cm to prepare a rope-shaped sustained release preparation. The amount of pheromone filling per 20a++ of this preparation is 106 ■, which is 5% of the filling amount before adjustment.
It was 9%. We also cut this sustained-release preparation and examined the cross-sectional area of the tube.

The variation was ±2%.

When the release rate of this sustained release preparation at 35°C was measured, although a decrease in the release period was observed, the release rate was almost the same as that before pressing.

Comparative Example 2 A high-density polyethylene tube with an average inner diameter of 0.48 mm, wall thickness of 0.3 mm, and length of 500 m, designed to have the same filling amount as that obtained in Example 1, was produced.
The obtained tubes had large variations in inner diameter and wall thickness, and also had large variations in cross-sectional area of ±18%, making them unsuitable as sustained-release preparations.

Furthermore, when this 500 m long tube was filled with sex pheromone by reducing the pressure at one end and applying a pressure of 3 kg/JG to the other end in the same manner as in Example 1, the time required for this was 7 hours, which is not practical. Ta.

Comparative example 3゜Same inner diameter as used in Example 2, 1.0 mm, wall thickness 0.3
+mm, the same amount (106,
) was filled with 8°10-dodecagenyl alcohol, and the release rate at 35°C of the obtained sustained-release preparation was measured, and the release rate was only about half that of Example 2. It was not suitable for practical use.

Example 3 Dextrolimonene: 659 parts by weight, β-hydroxyphenylethyl alcohol = 158 parts by weight, lilyaldehyde = 76 parts by weight, heliotropin = A 15 cm diameter container filled with a blended fragrance with a citrus floral aroma consisting of 76 parts by weight and 31 parts by weight of vanillin and controlled at 60°C.
Pressing was performed using a pair of rolls while changing the clearance in three stages to produce various sustained release preparations shown in the table below.

These tubes were sealed and cut using high-frequency heating in each of the 10 countries to form a tubular sustained release preparation, and the release rate at 40° C. was measured.

At this time, the filling amount could be arbitrarily changed while keeping the release rate approximately the same, and the effective release period could also be changed accordingly. Therefore, since tubes of other sizes are not required, the economical effect is also great. The results are also listed in the table below.

(Effects of the Invention) According to the present invention, (1) it is possible to fill a tube made of a polymeric material with a small amount of a volatile substance without impairing its performance as a sustained release preparation;

■ A tubular sustained-release preparation with high filling accuracy and uniform release rate of volatile substances can be obtained.

■When filling a tube with a highly viscous volatile substance, there is no need for overfilling as in conventional methods, and the process can be done with the minimum necessary amount.

■Enables the filling of volatile substances that could not be filled conventionally due to their high viscosity.

■Even if a design change is made to keep the outer surface area of a sustained-release drug constant and change only the filling amount of volatile substances, the filling amount can be adjusted using a press, so existing tubes can be reused and new tubes can be created. There is no need to create one. As a result,
It is possible to improve economic effects and expand the scope of application of sustained release preparations.

Patent applicant: Shin-Etsu Chemical Co., Ltd.

Claims (1)

[Claims] 1. A sustained release preparation prepared by pressing a tube filled with a volatile substance to adjust the filling amount. 2. The sustained-release preparation according to claim 1, wherein the volume of the volatile substance after adjustment is 95 to 10% of the volume before pressing. 3. The tube has an average inner diameter of 0.5 to 5 mm and a wall thickness of 0.1
2. The sustained release formulation according to claim 1, comprising a polymeric material with a thickness of ~3 mm.