JPS58189112A - Production of material containing physiologically active substance - Google Patents

Abstract

PURPOSE:A tightly sealed transferring machine that can continuously send the substance as the content is always made to renew its surfaces, is provided with a temperature-controling mechanism all over the transferring zone as well as a plurality of feed inlets is used to produce a material containing a physiologically active substance continuously without loss of the active substance. CONSTITUTION:A tightly sealed transferring machine that can continuously send the substance as the content is always made to renew its surface and is provided with temperature controlling mechanisms 9-15 all over the transferring zone and a plurality of feed inlets 2-6, e.g., a single-screw or double-screw extruder is used to feed a carrier containing a thermoplastic high molecular material capable of forming films and keeping their form and physiologically active substances to these inlets continuously. They are mixed in the machine under the tightly sealed conditions and the heating of the machine is controlled by means of the mechanisms all over the transferring zone to prevent the loss caused by evaporation and decomposition of the active substance, thus producing a material containing physiologically active substance alone or a combination thereof with a backing material 21 continuously with advantage.

Description

[Detailed Description of the Invention] A method for producing a bioactive substance-containing material (referred to as IJ.-F4 Makuden-containing Yanagi) and a nuclear production method that eliminates this loss. The present invention relates to a conventional method for continuously producing sheets or films containing bioactive 4B substances either alone or in combination with a backing material.

The present invention utilizes techniques to reduce the thermal densities during the production of the material, thereby eliminating the decomposition of physiologically active substances, and also to ensure uniform mixing within the closed system transfer device. The purpose of the present invention is to provide a method for continuously manufacturing #fiber-containing materials or #7 θΩ products by destroying 4R-occupied substances.

A barrel containing 4 raw active substances and a carrier that carries the substances in one bowl! The substance content to be extracted is obtained by adding a carrier by methods such as fg decomposition, mixing and polymerization, and emulsification, and adding a physiologically active substance to this.
The carrier made by the process of blending the mixture includes a stirring blade, a pot with a homogeneous mixer, a mixing roll, a bumper mixer, a pressure kneader, a kneader-ruder, etc. Mixing equipment is commonly used.

However, the addition process using the kettle mixer of C1 and C1 is an open batch process, and the heat during processing is υl.
Most of them are relatively sa =<, s
When arranging raw 4F'8 anastoelectrics, which are often dissipated, it is decided that it is uneconomical because it is necessary to mix in a glossy color to reduce losses due to r4Wi or thermal decomposition. There is a χ point that it is one female to provide an E-quality warehouse product that is consistent and uniform.

When the material containing material, which has been miniaturized by the Sashikuko LA self-zero method, is used alone or in combination with a backing material, the sheet material is made into a film using the above-mentioned material containing material t-solvent. Either dilute it and cast it on a mold release liner, or apply it to the backing material surface and then heat and dry it, or use a tie extruder or hot melt applicator as described above. Either roll it or roll it with a calendar roll, r,'/-
) In order to make the film into a film, the lover of the L C1 physiologically active substance is further aided by these heating processes.

On the other hand, chill glycol, e-menthol,
d/-Glaster, which uses a sex drug as a stimulant like camphor, absorbs the unflavored ingredients of public ml,
After mixing with - and then blending the drug to make a fiber-containing material, this is lined with a backing material such as small iron cloth and IC calender row/L.
Spread the material and apply it to make the material. th''''' - Due to the heating during the cloth, deterioration occurs in the series or decomposition of the L C drug, and the gelation is uniform. When calculating 4, take into account such losses or losses due to decomposition such as '&-' and Mouth, 1 = /j, Stish-N-Isoprene (or Petazier/) - Stish-/Block remaining combination like right heat 1 = T @
Note: He also proposes a method to make a spy/○ type machine/thread item by heating and dissolving the enostone and oil component, emulsifying it, and adding 1.1 or less of the following four ingredients. 'LC is here. In the O≧6 method, the temperature is generally raised to around 90°C due to the relationship between the boiling point of water and the solubility limit. Losses due to numbers, etc. are 2 times less if the company is exempt.

Accordingly, the first purpose of this book is to develop a method for producing a storage product that eliminates the loss caused by physiologically active cutting.
,ll! It's about the same thing.

The second and first object of the present invention is to provide a manufacturing method for continuously producing substances. The present invention provides a method for continuously manufacturing a 6-prong-containing H sheet or noilm by assembling the original material and a backing material.

The object of the present invention is to be able to continuously transfer the contents while transferring the contents to the surface, and to provide one feeder and one raw material supply port in the entire area of the transfer tube. Using the closed system transfer device 4 prepared above, a carrier containing a thermoplastic polymeric material having skin-forming ability and shape retention and a physiologically active substance are continuously fed into the transfer device from the supply port F, and The carrier and substance are homogenized in a sealed state while heating the entire area of the transferred area (for example, to a predetermined temperature). To explain the present invention in detail, it is possible to display the internal objects] Button V!
Transfer while praying, ``With one gun, I'm going to cover the entire area of the 4-way process.''
Once the IIJ is discharged into the closed system transfer device,
According to the Ik terminal proboscis product number C, the actual and physiologically active substances are sequentially fl
Continuously supply from the H supply port, mix the contents uniformly in a closed system in the preset transfer 4, and transfer the contents containing c#kJ value. By applying one method of the present invention, the present invention provides a method for making all the products.In fact, nothing can be manufactured with closed threads, and the contents can be mixed uniformly while renewing the surface. This is due to the fact that the heat damage 11 (@ product of degree x time) that is individually suffered during production is small, and there is almost no change in quality due to volatilization or decomposition of physiologically active substances during production.

Because Saraki & Gouko-kashi partially processes the contents that are small in size using the screw in that part, it has the special feature of requiring less power and allowing the equipment to be made more compact.
IJ, one line of the manufacturing method of the present invention is shown using the drawings below.

The drawing shows the cross-sectional structure of a single-screw extruder, which is an example of a closed system transfer device used in the present invention.
A main supply port 2 is provided for supplying a carrier containing a thermoplastic polymer material having skin formation and shape retention ability or a portion of a physiologically active substance, and an extrusion die 16 is provided at the other end. 3s 4s 5 and 6 have supply ports, and as shown in the figure, the main supply port 2 is 1-, and the supply ports 3.4.57i and 6 are provided at approximately equal intervals. However, if it is lined up, it will be necessary to select an appropriate combination of concentration in the vicinity of the main supply port 2, which will mix everything in the early stage of supply.

The die 16 marked with # is continuously supplied with the substance-containing material C from the extruder, and is further continuously supplied with the substance-containing material alone or in combination with the punching material 21 to form a material-containing sheet or film 1'. The die 16 is removed and the substance-containing wood can be obtained from the outlet A of the C1 barrel 1.

Inside the barrel 1, several screws 8a, 8b, 8c, 8a and 8e are attached to the rotating shaft center 7. Scree-8a,--- of T et al.
When combined, Risky-8a, ---+ζL is the main supply port 2.
~ 6, the ``fkJ quality inclusions'' are transferred, retained, and reversed by the rotation of the axis 7, mixed, and advanced by 6 screws 8'% I: Inside of barrel 1 and The spacing is designed to increase miscibility, but it is generally set to 0.5 to 2 spacings.

9. 10% 11. 12. 13. 14 and 15 are all parts of the barrel 1 and the die 16Ke, n running heat limiter, and each part Kj is appropriate! lF1. It is said that the structure can control the heating evenly over the entire length.
Of course, it is possible to make it a II configuration.

In addition, 18, 19, 20, 21 and 22 in the figure are barrel 1
The substance-containing material extruded from the extrusion port 17 of the die 16 attached to the outlet AK@ is combined with the backing material 21 (a round substance-containing sheet or tape B,
18 is a pack roll, 19 is a bonding roll, 20 is a guide roll, and 22 is a film formed on the surface of the backing material 21 and attached to the surface of the 9m'jit body-C.
It is a similar proboscis product of Jtrl, n, 6#, which is configured like Iu h,
For example, first, an arbitrary carrier is continuously supplied from the main supply port 2, and a formulation including a physiologically active substance is sequentially and continuously supplied from the supply ports 3.4, s and 6, --Transfer and mix uniformly while renewing the surface of the contents in the first rotation, create a homogeneous physiologically active substance jltA compound in a closed system inside the machine, remove and remove the physiologically active substance jltA from white A. Take out 1 cup of active material (or (^l) Put die 16 into the opening A of the active material and form the sheet into a film, and the plastic film V is a sheet or a non-woven fabric. The book can be laminated with a covering material 21 such as cloth, foamed film or sheet.

In addition, in the example shown in E, using a Tsumugi Scree extruder, C
However, it is logical that it can be mixed in the proboscis-1 by using a twin-screw extrusion machine and operating the 4F mark and the four keys.
[Rudeme / 5 pieces] One-sleeve mata / double-shafted oak sufu 17 W-press"b* (C) is as described above, the distance between the screen and the Banol inner box is preferably 1fiO65-21 Although it is designed to have 111 pi degrees, the speed of U = y distribution, that is, (Enji Akira (→/Number of laterals x screenie outer diameter/f''j between screen and barrel)
[) is generally preferably designed to have a nC of 1000/min or more.

In addition, the transfer device used in the present invention is a closed system, and the surface of the inner grain is constantly updated by the action of the screw and barrel, and the Ca content is continuously transferred over the entire area during the 4 hours of transfer. As long as it has a control mechanism and a plurality of supply ports, it can be used without being jetted into the above-mentioned two-wheel or two-wheel screw extruder.

In the manufacturing method described in E, the key to obtaining the desired physiologically active substance-containing product using the transfer device is, of course, to select the properties and supply position of the carrier and physiologically active substance supplied from the supply port. It is important to control the viscosity of the contents inside the barrel by controlling the temperature of each part of the rc barrel, and if this viscosity control is insufficient, the contents may backflow or become uneven. There is the disadvantage that only substances containing substances can be obtained.The preferred viscosity for stable transfer depends on the width and size of the transfer device, the gap between the barrel surface and the screw, the type and viscosity of the carrier, the transfer speed of the contents, Although it varies depending on the properties of the target physiologically active substance mixture, it is generally in the range of 100 to several tens of thousands of poise.

Next, carriers and physiologically active substances used in carrying out the present invention will be explained.

The carrier is a parent component of the physiologically active substance and contains raw J! It is intended to be a carrier component that maintains active substance #II in a dissolved or uniformly dispersed state.

As mentioned above, the final shape of the material-containing material may be formed into a sheet or film by using the material-containing material alone or in combination with a backing material, or by molding the material-containing material into a predetermined shape K, for example, in the shape of an animal or plant. Therefore, the thermoplastic polymeric material that is the main component of the C1 carrier contains at least a skin. A polymer material having forming ability and shape retention ability is selected.

As the thermoplastic polymer material, thermoplastic polymers such as styrene-in-place styrene block copolymer, styrene-butadiene-styrene block copolymer, trans-inoprene, and ethylene-vinyl acetate copolymer are preferably used. However, other acrylic copolymers, polyethylene,
Thermoplastic polymeric materials such as polypropylene can also be used.

These polymeric materials can be packaged in any form such as powder, pellets, or water dispersion. The preferred elastomer has a tensile strength comb ITMD41 of over 5Ky/d bJ.
2), and such a tensile strength is preferable since it will not unnecessarily break when formed into a film or sheet depending on the material content.

Carrier components that may be used as necessary together with the thermoplastic polymer material listed in E include a tackifier that is in the form of IIA'1 at room temperature, a tackifying substance that is in a liquid or semi-solid state at room temperature, and There are known compounding agents.

Adhesive material that is solid at room temperature! R fats include natural resins such as gum rosin, wood rosin, and dammar, modified rosins such as polymerized rosin, partially hydrogenated rosin, glycerin ester rosin, pentaerythate ester rosin, and e.
derivatives of n et al., polyterpene resins, xylene bridges,
Examples include petroleum resins, styrene fruit resins, coumaron indene resins, and fat-reduced saturated hydrocarbon water-wood S resins.

Additives, usually in liquid or semi-solid form, include rosin resins such as rosin methyl ester, hydrogenated rosin methyl ester, rosin triethylene glycol ester, hydrogenated rosin triethylene glycol ester, rosin diethylene glycol, softening Ki/ren type m with rose below 30℃
Polyterpene-based liquid #9, low molecular weight tII such as dibutyl phthalate and dioctyl phthalate
I plastic moe, machine oil, cylinder oil, transformer oil, rosin oil, Suhi' 7 dollar Lm Q loki 1 Il I If J% e @f1. @ Paraffin, prohyde oil, vegetable oil, waxes, low molecular weight polyisobutylene, low molecular weight Polyethylene, borigtene 1. Nocturnal polybutadiene, etc.
Ru.

Other compounding agents for ε include C1 polyethylene glycol oleyl needle, polyethylene glycol, nonylphenyl ether, polyethylene glycol decylphenyl ether, sorbitan monolaurate, etc. as surfactants when converting yarn into Ichiryu di-N. However, as a filler for the purpose of compaction and prototype - calcium chloride, clay,
Merck, titanium white, silica, etc. are used, as well as colorants, stabilizers, anti-aging agents, etc.

These carriers are appropriately selected depending on the properties of the desired final product containing a physiologically active substance, and when the material is designed to have pressure-sensitive adhesive properties, the carrier is compatible with the polymeric material. It is preferable to mix the tackifying resin and/or the additive substance, which are solid at room temperature, in a ratio of 1:0°1 to 10 (weight ratio). When designing an adhesive substance, the polymer material, the oil in the additive substance, the surfactant, and water are added to 100 parts by weight of the polymer material (preferably elastomer). 5~301i part and 1~
The amount of water is 201 parts by weight, and the water is added so that the proportion of water particles in the W10 emulsion is 80% or less.

Mosquito W/O type emulsion pressure-sensitive adhesive material is extracted from the transfer device or die and cooled to a room arc region to gel, and a physiologically active substance is supported in the hydrous gel. A physiologically active substance-containing substance is obtained, which is a biologically active substance supported on the carrier that has a biologically active function of Q1, and C is a biological IC rod. There is a distinction between substances that are physically acceptable and substances that are physically acceptable.
Ru.

Biologically acceptable physiologically active substances are substances that ooze out onto the surface of a substance-containing substance or are released into the air when the substance-containing substance is placed in a specified usage environment, whether in a closed system or an open system. It is a substance that destroys the target young fruit by 4F3, such as insecticides, fungicides, leather removers, plant growth promoters, growth inhibitors, nutrients, etc. Dry medicine, plant hormones,
Animal hormones, animal pheromones, rust inhibitors, anti-mold agents, fragrances, etc. can be tasted.

The pill is pharmacologically released to dissolve physiologically active substances, and the management fV
’Lfit K locally or far from the management position
An organic or inorganic pharmacological compound that exerts a systematic pharmacological effect at the jn9 position, such as a sleeping agent, a sedative, a tranquilizer, a spasticity suppressant, a muscle relaxant, an anti-inflammatory agent, an antipyretic agent, Inflammation treatment agents, intervening anesthetics, antidepressants, tumor healing agents, vasodilators, hormonal agents, cardiovascular agents, diuretics, sympathomimetic stabilizers, hypoglycemia treatment agents, a [drugs, Anti-inflammatory analgesics, etc. are used.

Therefore, as mentioned above, the production method of the present invention is capable of producing substances contained in physiologically active substances in a short time under controlled temperature conditions and in a sealed state. Salicylic acid ester, e-menthol, dIl! can significantly reduce the loss.
It is understood that this is particularly useful when using anti-inflammatory analgesics as a physiologically active substance and sipping l-camphor, which generally causes large losses during the manufacturing process. The manufacturing method of the 1b wax 1, + corner will be explained below in terms of the actual example of the construction frame, but 2 the present invention is not limited to the following example of the turret. ，
In less than one fruit lIA the same, the middle part of the length and % are '! ! It is assumed that r1″L also means the jusun menacing position.

Pricing fee 1 SklJ, outer diameter 40mm, barrel strength 2160mm, gap between barrel and scree 1°001! In III, when the total temperature of 1 to Vl]-n in the attached gap is controlled at 70°C, the main supply port 2 is Ethylene-vinyl acetate co-electric composite pellets '4r containing 33% vinyl acetate were continuously supplied from the feed port 6 at a rate of 3 Kg/min. -858/'A) at 0.6Kl/mi
Continuously supply the mixture at a ratio of n [uniformly - t], and immediately after taking out the lemon*flavor-containing mixture from the take-out port A (the mixture C was mixed to a thickness of Zoo) 1° on the surface of a polyester film of tm. The amount of fragrance per unit volume of the core sheet (measured #L) was 16.
42%, and there was almost no polishing compared to the 16°67% of the embedded brass mixture.

Gee 4 Shichirinri 2 Screw outer diameter 5〇-zen, barrel width 2160' in
a+.

With a gap of 1° Oam between the barrel and the scree, 1 to [=170°C, I=140”C1ff-1 in the attached drawing
204c, V-100℃, Vl ~ W = 90℃ text ff ~
■=80℃ and 62800/w
Using a nine-screw extruder with a speed gradient of
1,150,000 styrene-butadiene-styrene block copolymer was continuously fed at a ratio of 16679/rn1n, and polyisobutyne with an average molecular weight of 1260 was fed from the lower common feed port 3 at 1'J with a viscosity of 167 min/min. 350 Saybold paper liquid paraffin at a ratio of 333j'/win, polyterpene type 41 with a softening point of 115°C is fed from the supply port 4 to fat t 1 a a 3? /m1n1 From the supply port 6, a mixed drug of monoglycol salicylate: l-menthol = 1:1 was continuously supplied at a ratio of 33497ml.
The mixture was mixed uniformly to produce a plaster body.

This paste was laminated to a thickness of 200.4 FB on one side of a polyvinyl chloride film with a thickness of 120 μm as a backing material using a die 16 as shown in the figure, and a release film 22 was temporarily attached to it, and the film was continuously laminated. plaster
1li zoushimaru.

This plaster has sufficient pressure-sensitive adhesive properties, has a monoglycol salicylate content per unit volume (measured menthol content is 4°29% (theoretical content is 4°36%),
The loss of drug is almost negligible.

Practical 3 Combined scree outer diameter 5Qaa, barrel [S216
0m1. Gap between barrel and scree 1.001111
Then, a twin-screw extruded rock with a zone arrangement approximately the same as that shown in the attached drawings (1 time, ■ ~ II = 200 °C, f = 140 °C
, IV=95℃, V=85℃%VI-80℃, ■～■=
85℃, speed gradient fji! 31400/m1n), styrene-isoprene-styrene/block #cte body with a styrene content of 14% and an f-average molecular density of 125000 was continuously supplied from the supply port 2 at a rate of 264° 5f?/min. Then, from the supply port 3, the melted alicyclic saturated hydrocarbon having a softening point of 100°C was fed at 285°7/rn.
In the feed port 4, paraffin having a viscosity of 55 Seigilt seconds was added at a ratio of 248°3 iP/m 1 n and sorbitan monooleate 58.5 n/rB i ,n from the feed port δη. 445.5 iP/m i of water
20 parts of glycol salicylate from lIC1 supply port 6, l
- Mixed drug consisting of 3 parts of menthol, 3 parts of a/-force/fur and 1 part of thymol at 58.2? /min to produce a W/○ type emulsion pressure-sensitive adhesive bag material.

This paste was pressed onto one side of a polyester non-woven fabric with a basis weight of 130 mm and a die 16 as shown in the figure.
A cataplasm was continuously produced by applying the product using a 700-voice I.V. and attaching a release film to it, and cooling it in the room to gel it.

This backing agent is a pressure-sensitive adhesive type that has a sufficient cooling sensation and # & coral effect, and has II'#! The loss of J is as shown in Table #I1. Note that the reference content values in Table 1 are the measured amounts of the drug concentration of the acid compound for plaster sampled from the outlet A of the extruder.
(Position /P) Real 1ilii row 4 2 pieces combined; Scree outer diameter 50ol I111 Barrel length 2160mm, gap between /: L/A/ and Scree knee 1. OQmm, two-axis screen with zone arrangement approximately the same as the attached drawing.
5700/man), and provided @LI2.・No・ra、
10 (H'/ At a ratio of n; A 9:1 dispersion was mixed uniformly at 20j'/min to form a C1 pharmaceutical preparation compound, which was then mixed using a die 16 to form a powdered material. 40 pages on a polyethylene film with a thickness of 80 μm for binding C.
s (Dli) and irradiated with ultraviolet rays for 3 minutes using a 400 W high-pressure mercury lamp (distance @ 10 cm) with a wavelength of 2800 A on the surface to continuously produce an anti-inflammatory pharmaceutical preparation. The formulation had sufficient skin adhesion and was readily absorbable through the skin, with almost no drug loss during the manufacturing process.

As is clear from the above examples, by applying the production method of the present invention, it is possible to reduce the loss of the physiologically active substance and reduce the amount of C, thereby providing a physiologically active substance-containing product.

[Brief explanation of the drawing]

The diagram shows the single-screw extruder used in the present invention, 4/f maker, Nitto lK Industrial Co., Ltd. representative, ± 6 three parts.

Claims (1)

[Claims] 1) Continuously transfer the contents at υiε while updating the torsional surface, and over the entire area of the above transfer 184! A closed system transfer system 4 is used, which has a raw material supply port with a number of layers of 1-, and a thermoplastic polymeric material having the ability to form a skin and form a layer is contained in this transfer device. The carrier and the physiologically active substance are continuously supplied from the supply port indicated by L, and the carrier and the substance are uniformly mixed in a sealed state while controlling heating to a predetermined @ Violet with M) over the entire area of the transferred IM root. A method for producing a product containing four active substances, which is characterized in that the product is taken out from a transfer device automatically. 2) The closed group transfer device is a single-screw or twin-screw type scree extruder.Claim 1.The device is made of the raw material that can be used in the same way as described in Claim 1.Claim 11. The manufacturing method of 4 raw active substances "Sakura Yumono". 5) The manufacturing method of the physiologically active substance-containing product described in each of Items 1 and 3 above. 5) The physiologically active substance is a pharmaceutically acceptable drug.
Iif'F Required Range The angle of the physiologically active substance described in item 1
How to make the snout. 6) Claim 5LJi in which the drug is an anti-inflammatory drug
A method of manufacturing a substance containing the 4 life notes of a thief.