JPH01268630A - Sustained release pharmaceutical - Google Patents

Abstract

PURPOSE:To obtain the subject pharmaceutical, containing a drug effective ingredient in a filmy substrate consisting of a specific polyvinylpyrrolidone polymer and specified vinyl acetate polymer and capable of sustainedly releasing the drug effective ingredient for a long period without any sense of incompatibility in use. CONSTITUTION:A pharmaceutical obtained by containing a drug effective ingredient in a filmy substrate constituted of a substance in a homogeneous state of a polyvinylpyrrolidone polymer having 50,000-1,800,000, preferably 200,000-1,000,000 weight-average molecular weight and vinyl acetate polymer having 25,000-500,000, preferably 40,000-130,000 weight-average molecular weight. The ratio of the above-mentioned polyvinylpyrrolidone to the polyvinyl acetate used is preferably within the range of 2:8-8:2, especially within the range of 3:7-7:3. In preparing the pharmaceutical, the afore-mentioned polyvinylpyrrolidone and polyvinyl acetate are dissolved in a solvent and the drug effective ingredient is then added and mixed therewith. The resultant solution is subsequently cast on a releasable liner, dried and formed into a film to afford the aimed pharmaceutical.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a sustained-release preparation that is applied to the oral cavity and used for gradual and long-term administration of drugs in the oral cavity.

[Conventional technology]

Conventionally, the methods of administering drugs in the oral cavity include liquid preparations,
Those using ointments, troches, buccal tablets, sublingual tablets, etc. are known. Recently, oral preparations such as Trackfield-type tablets that reduce discomfort in the oral cavity have been developed as intraoral sustained-release preparations (Japanese Patent Application Laid-Open No. 55-59109, JP-A No. 58-154547, JP-A-58-1989). 154548
(see JP-A-61-15829, JP-A-61-175), sustained-release nifedipine tablets containing nifedipine and applied to the oral mucosa
(see Publication No. 10), etc. have been devised. In addition, as a film-like drug aimed at reducing discomfort in the oral cavity, an oral mucosal patch preparation containing a drug in a water-soluble film (see JP-A-61-280423)
has also been devised.

[Problem that the invention seeks to solve]

However, the above-mentioned oral preparations cannot simultaneously satisfy both the sustained release of the drug and the discomfort of the preparation in the oral cavity during use. For example, liquids, ointments, and the like are easily washed away by saliva and other moisture in the oral cavity, making it difficult to maintain their medicinal efficacy over a long period of time. In addition, lozenges are made by mixing drugs with a base such as saccharide and compressing them into large tablets, which causes a great discomfort when used. On the other hand, buccal tablets and sublingual tablets are usually intended for rapid absorption of drugs through mucous membranes and cannot be called sustained-release preparations. On the other hand, although the Trackfield type tablets exhibit sustained drug release properties, their thickness as tablets is as high as 1.3 to 3M, resulting in poor flexibility and discomfort during use. In addition, the above-mentioned oral mucosal patch preparation containing a drug in a water-soluble film is flexible and does not cause discomfort when used, but because the film base material is water-soluble, it is easily absorbed by saliva and other moisture in the oral cavity. The film dissolves during treatment, which poses a problem in terms of the sustainability of the drug's efficacy in the oral cavity. The reality is that no drug has yet been developed that simultaneously provides the two features of minimal discomfort during use and the release of medicinal ingredients over a long period of time.

The present invention was made in view of the above circumstances, and aims to provide a sustained-release preparation that causes less discomfort during use and allows medicinal ingredients to be released from a film-like base material over a long period of time.

[Means for solving problems]

In order to achieve the above object, the sustained release preparation of this invention
A sustained-release preparation consisting of a film-like base material containing a medicinal ingredient, wherein the film-like base material has a weight average molecule!
! 50,000 to 1,800,000 vinyl pyrrolidone polymer and weight average molecular weight 25,000 to 500,00
0 vinyl acetate polymer.

[Effect]

That is, the present inventors conducted a series of studies on a base material that causes less discomfort when used in the oral cavity and can gradually disintegrate over a long period of time to release medicinal ingredients over a long period of time. As a result, a specific molecular weight region of vinyl pyrrolidone polymer, which is a water-soluble polymer, and a specific molecule ff1j of vinyl acetate polymer, which is a water-insoluble polymer,
When using a homogeneous mixture of Jt range materials,
The present inventors have discovered that it is possible to obtain a sustained-release preparation that simultaneously satisfies the following two points: less discomfort during use, and the ability to gradually disintegrate and release medicinal ingredients over a long period of time. When the sustained-release preparation of the present invention is inserted, for example, into the southern part of the maxillary anterior teeth, the film-like base material gradually disintegrates with saliva and moisture in the oral cavity, diluting the medicinal ingredient and exerting a long-term medicinal effect. At this time, since the film-like base material is a flexible film, it has excellent adhesion to the oral mucosa and hardly causes discomfort during use. Although the sustained-release preparation of the present invention gradually disintegrates and releases the medicinal ingredient into the oral cavity, the disintegrated base component is swallowed together with saliva. However, the base material components are harmless even if swallowed.

In addition, when the vinyl pyrrolidone polymer and the vinyl acetate polymer are in a homogeneous state, the above-mentioned components constituting the film-like base material are
It indicates a state in which the components are homogeneously mixed with each other in a molecular state, and means that each component does not exist partially independently in a film-like body.

The film-like base material used in the sustained-release preparation of this invention is:
As mentioned above, it is obtained using a specific vinyl pyrrolidone polymer and a specific vinyl acetate polymer. Even if component raw materials other than these are used, it is almost impossible to obtain a film-like base material in a homogeneous state.

The specific vinyl pyrrolidone polymer has the effect of disintegrating the film-like base material by saliva and other moisture in the oral cavity, and has a weight average molecular weight (hereinafter referred to as r).
(abbreviated as M W J) 50,000 to 1,800,000
, more preferably 200,000 to 1.000,000
are used. Examples of the vinyl pyrrolidone polymer include vinyl pyrrolidone homopolymer (hereinafter referred to as "polyvinyl pyrrolidone"); however, it is not limited to homopolymers, and includes vinyl pyrrolidone-vinyl acetate copolymers containing vinyl pyrrolidone as a main component; Also included are vinylpyrrolidone copolymers such as acrylic acid-vinylpyrrolidone copolymers containing vinylpyrrolidone as a main component.

The specific vinyl acetate polymer has the effect of extending the disintegration time of the film-like base material, regulates the disintegration of the polyvinylpyrrolidone, and causes the film-like base material to gradually disintegrate. . The vinyl acetate polymer used has a Mw of 25.000 to 500,000, more preferably 40.000 to 130.000. The above-mentioned vinyl acetate polymer includes not only vinyl acetate homopolymer (hereinafter referred to as "polyvinyl acetate"), but also ethylene-vinyl acetate copolymer containing vinyl acetate as the main component, and polyvinyl acetate copolymer containing vinyl acetate as the main component. Also included are vinyl acetate copolymers such as acrylic acid-vinyl acetate copolymers.

However, the preferred one is 1. It is a vinyl acetate homopolymer.

The above polyvinylpyrrolidone (X) and polyvinyl acetate (Y
) usage ratio is based on weight, X:Y=2:8~8:2
A range of is preferred. Furthermore, from the viewpoint of the homogeneity of the film-like base material and the disintegrability of the film-like base material, 3 near to 7:
3 is more preferred. In this way, by changing the usage ratio of polyvinylpyrrolidone and polyvinyl acetate within the above range, the disintegration time of the film-like base material can be adjusted, and the release rate of the medicinal ingredient contained therein can be jM fJff. .

Moreover, in this invention, for example, a plasticizer may be used in addition to the above-mentioned raw materials.

Examples of the above-mentioned plasticizers include dimethyl phthalate, dibutyl fucrate, glycerin monolithylate polydiethylene glycol, glycerin diaceto monolaurate, and glycerin monoaceto monostearate.

Such a plasticizer is preferably set within a range of 1 to 50% by weight based on the solid content of the film-like base material.

Such sustained release preparations can be obtained, for example, as follows. That is, polyvinylpyrrolidone and polyvinyl acetate are dissolved in a solvent, preferably a common solvent for both, and then a medicinal ingredient is added and mixed. It can be obtained by casting this on a releasable liner and drying it to form a film. Moreover, it is also possible to adjust the thickness of the film-like base material by laminating film-like base materials that have been dried and formed into a film onto each other.

The above solvents include alcohols such as methanol and ethanol, mixed solutions of water and alcohol such as water and methanol, water and ethanol, chlorinated hydrocarbons such as methylene dichloride and chloroform, amines such as butylamine, and nitrohydrocarbons such as nitromethane. Examples include paraffins.

The liner may be any suitable film such as release-treated polyethylene laminate paper, polyethylene film, siliconized polyethylene terephthalate film, or the like.

Examples of the drying method include a method using a high-temperature air bath using a dryer, a drying tower, etc., a method using a vacuum dryer, and the like.

In this way, the sustained release formulation of this invention is obtained. The thickness of this preparation is not particularly limited, but it is preferably 10 to 2,500 μm in order to obtain practical sustained release properties, and although it varies depending on the amount of medicinal ingredient contained, it is 100 μm in consideration of discomfort when used in the oral cavity and ease of handling. ~1000 μm is more suitable.

The medicinal ingredients contained above include systemic drug 2.
Examples include topical drugs, fragrances, and other substances that have deodorizing effects. Such medicinal ingredients may be solid or liquid at room temperature, as long as they can be dissolved or uniformly dispersed in the mixture of polyvinylpyrrolidone and polyvinyl acetate. More preferably, it is soluble in a co-solvent of polyvinylpyrrolidone and polyvinyl acetate.

The above-mentioned systemic drugs include general anesthetics, hypnotics, sedatives, antiepileptics, stimulants, stimulants, sedatives, psychoneurotic drugs, muscle relaxants, autonomic nervous drugs, antispasmodics, and antiparkinsonian drugs. , antihistamines, stimulation therapy agents, allergy agents 1 cardiotonic agents, arrhythmia agents, diuretics, antihypertensive agents, vasoconstrictors, coronary vasodilators, peripheral vasodilators 2 arteriosclerotic agents, other circulatory organ agents, respiratory agents Accelerator, antitussive expectorant, peptic ulcer treatment, other gastrointestinal agents, pituitary hormone preparation.

Thyroid and parathyroid hormones, androgenic hormones, follicular and progestin hormones, other hormones, uterine contraction agents, urogenital agents, enzyme preparations, antidiabetic agents, other metabolic drugs, anti-malignant III tumor agents, antibiotics, chemotherapeutic agents,
Maya et al. The compounding layer of such systemic drugs varies depending on the type of drug, but usually 0.0. OO1~
It is preferable to set the amount to 50% by weight, preferably 0.5 to 30% by weight.

In addition, the above-mentioned topical drugs include adrenal corticosteroids,
Anti-inflammatory agent, bactericidal agent, analgesic agent, hemostatic agent 2 vasodilator 9 tissue repair agent, antiviral agent, bone metabolism agent.

Examples include astringents.

Further, examples of fragrances and other substances having a deodorizing effect include fragrances such as peppermint oil, spearmint oil, peppermint oil, and citrus oil, and substances having a breath odor removing effect such as green tea flavonoids and chlorophyll.

Furthermore, by laminating a water-soluble film containing the same medicinal ingredient on a sustained-release preparation containing the same medicinal ingredient, it is also possible to obtain a formulation having two levels of release rate of the medicinal ingredient. In other words, the easily water-soluble film is quickly dissolved by saliva and other moisture in the oral cavity, so the medicinal ingredients in the easily water-soluble film are quickly released, and then the sustained-release preparation of this invention is gradually released. This is because the medicinal ingredients in sustained release preparations are gradually released due to disintegration.

Further, the sustained-release preparation of the present invention can be made into an intraoral adhesive preparation by laminating it with a material that can adhere to the mucous membrane in the oral cavity.

The above-mentioned materials that can adhere to the oral mucosa include JP-A-61
Examples include those disclosed in Publication No. -249472 and the like.

In the sustained-release preparation laminated with the film-like adherent described in the above-mentioned publication, the sustained-release preparation portion comes into contact with saliva and gradually disintegrates, releasing the medicinal ingredient over a long period of time.

〔Effect of the invention〕

As described above, the sustained-release preparation of the present invention is a homogeneous product of specific polyvinylpyrrolidone and polyvinyl acetate, and is flexible because it is composed of a thin film-like base material containing a medicinal ingredient. It causes little discomfort during use and has excellent adhesion to the oral mucosa. In addition, since the film-like base material gradually disintegrates due to saliva and other moisture in the oral cavity, the medicinal ingredients contained therein are sustainedly released to the application site over a long period of time and can exert medicinal effects.

Next, examples will be described together with comparative examples.

[Experimental Example 1] Polyvinyl acetate (Mw = 69,000) 50 parts by weight (
(hereinafter abbreviated as “part”) and polyvinylpyrrolidone (Mw=1
, 200,000) and 250 parts of methanol were mixed with 2 parts of Food Red No. 102 dissolved in a small amount of methanol, and this was cast onto the treated surface of a polyethylene laminate paper that had been subjected to release treatment. By using a dryer, it quickly dries into a film with a thickness of 600 μm.
A sustained release model formulation of m was obtained. This was cut into 1 cm square pieces to obtain test pieces, and an underwater release test was conducted as shown below, with the results shown in FIG. 1 being obtained. the result,
The release of Food Red No. 102 from this sustained release model formulation showed sustained release properties.

<Water release test method No. 1> 20 d of distilled water kept at 37°C was placed in a 50 m1 Erlenmeyer flask with a stopper, and one side of a test piece of a sustained release model formulation was fixed to a phenol resin board with double-sided adhesive tape. The sample was immersed with the sustained release model formulation side up, and the Erlenmeyer flask with a stopper was immersed in a constant temperature bath at 37°C. After a certain period of time, the distilled water was filtered with a membrane filter, and the absorbance of 500 parts w was measured using a spectrophotometer to obtain the release rate of Food Red No. 102.

[Experimental Example 2, Comparative Experimental Examples 1 to 5] Using the water-soluble polymer and water-insoluble polymer shown below, 6
A 1:1 mixture sheet of various water-soluble polymers and water-insoluble polymers was prepared by the following method. 2 parts of Food Red No. 102 dissolved in a small amount of methanol in a mixture of 50 parts of a water-soluble polymer and 50 parts of a water-insoluble polymer dissolved in 250 parts of methanol (500 parts only for Nisso I1.P C-H) The mixture was mixed and cast onto the treated surface of a polyethylene laminate paper that had been subjected to release treatment, and quickly dried to form a film using a drier to obtain a mixture sheet with a thickness of 600 μm. The resulting mixture sheet was subjected to the above-mentioned underwater release test method No. 1 to obtain a release rate of food red No. 1.02 (see Figure 2).

(Water-soluble polymer) a: Human U-xypropylceltos (manufactured by Nippon Soda Co., Ltd.,
Nisso HP C-L) b: Human xip D bilseltos (manufactured by Nippon Ntasha, 8e) i PCI-1)
C: Methyl vinyl ether maleic anhydride copolymer (G
Manufactured by AP, Gantolets AN-119) d: Polyvinylpyrrolidone (manufactured by GAI, Ni-90) (water-insoluble polymer) e: Hydroxib U methylcell - sphthalate
(Shin-Etsu Chemical M, IIP-55) f:, f'J vinyl acetate (Mw=8600) g:f vinyl acetate (Mw=690000) (mixture sheet) Comparative experiment example 1 : a+f...A sheet comparative experimental example 2: b+g...B sheet comparative experimental example 3: c+g...C sheet comparative experimental example 4
: d+e...D sheet comparison experiment example 5: d+f...E sheet experiment example 2
: d+g...F sheet From FIG. 2, it was observed that the second experimental example made of polyvinylpyrrolidone and polyvinyl acetate exhibited sustained release of Food Red No. 102, and high reproducibility.

<Comparative Experiment Example 6> A solution of 50 parts of polyvinyl acetate (Mw = 69,000) and 50 parts of ethyl acetate and 50 parts of polyvinylpyrrolidone (Mw = 1,200,000) were mixed with 10 parts of distilled water.
2 parts of Food Red No. 102 dissolved in a small amount of methanol was mixed with a solution dissolved in When used, it was rapidly dried and formed into a film to obtain a sustained release model formulation with a thickness of 600 μm.

The obtained sustained-release model formulation was inferior in homogeneity to the sustained-release model formulation of Experimental Example 1 prepared using a co-solvent.

Experimental Example 3> 60 parts of polyvinyl acetate (Mw=69,000) and polyvinylpyrrolidone (Mw=1,200,000)
40 parts were used. Other than that, a sustained release model preparation with a thickness of 600 μm was obtained in the same manner as in Experimental Example 1.

The obtained sustained release model formulation was subjected to the above-mentioned underwater release test method N.
The release rate of Food Red No. 102 was measured according to α1. As a result, the release of Food Red No. 102 showed sustained release (see Figure 3).

Moreover, from the results of Experimental Examples 1 and 3, it can be seen that the release rate changes when the mixing ratio of polyvinylpyrrolidone and polyvinyl acetate is changed. From this, it is considered that in the sustained release preparation of the present invention, the release rate of the medicinal ingredient can be easily controlled by changing the mixing ratio of polyvinylpyrrolidone and polyvinyl acetate.

[Comparative Experiment Example 7] Polyvinylpyrrolidone (Mw = 1,200,000)
Only 100 parts were used. Other than that, a sustained release model formulation was obtained in the same manner as in Experimental Example 1, and an underwater release test was conducted. As a result, the obtained sustained-release model formulation dissolved in about 10 minutes,
It did not show sustained release properties.

[Comparative experiment example date]

Only 100 parts of polyvinyl acetate (Mw=69,000) was used. Other than that, a sustained release model formulation was obtained in the same manner as in Experimental Example 1, and an underwater release test was conducted.

As a result, the release rate of Food Red No. 102 after 24 hours was 2.
The utilization rate was low, ranging from 0 to 30%.

[Example 1] Polyvinyl acetate (Mw - 69,000) G 0 part and polyvinylpyrrolidone (Mw = 1,200,000)
40 parts of sodium guaiazulene sulfonate dissolved in a small amount of methanol was melted and mixed with 250 parts of methanol, and this was cast onto the treated surface of a polyethylene laminate paper that had undergone release treatment, using a dryer. It quickly dries into a film with a thickness of 600 μm.
A sustained release formulation of m was obtained. The obtained sustained-release preparation was cut into 1 cm square pieces to prepare test pieces, and a discomfort window during use and an underwater release test were conducted using the following test methods.

[Conventional example]

Azunol 37 tablets (manufactured by Nippon Shinyaku Co., Ltd.) were used as a comparison product.

<Uncomfortable feeling during use> Using the obtained sustained release preparation and 37 Azunol tablets (manufactured by Nippon Shinyaku Co., Ltd.), each was inserted into the maxillary anterior teeth of 10 volunteers to investigate the discomfort during use. The results are shown in Table 1 below.

(Leaving space below) ■--21 jl- <Water release test No. 2 > Pour 20 d of distilled water kept at 37°C into a 50 d Erlenmeyer flask with a stopper, and add a test piece of sustained release preparation (or Azunol 37 One side of the tablet (tablet) was fixed to a phenolic resin plate with double-sided adhesive tape, and the sample was immersed with the sustained-release formulation side (or Azunol 37 tablets) facing up, and placed in an Erlenmeyer flask with a stopper in a constant temperature bath at 37°C. Soaked. After a certain period of time, the distilled water was filtered with a membrane filter and measured with a spectrophotometer.
The absorbance at 5 nm was measured to obtain the release rate of sodium guaiazulene sulfonate. The results are shown in FIG.

In addition, in FIG. 4, A corresponds to the sustained release preparation and B corresponds to 37 Azunol tablets.

From the above results, Example 1 product has a thick Azunol 3
Compared to 7 tablets, there was less discomfort, and despite the thinner thickness, the release of sodium guaiazulene sulfonate was sustained, and the same duration as Azunol 37 tablets was observed.

[Examples 2 to 7] Polyvinyl acetate (Mw = 69.000) and polyvinylpyrrolidone (Mw = 1,200,000) were used in the ratios shown in Table 2 below. A sustained release preparation was obtained in the same manner as in Example 1 except for the above. The obtained sustained release preparation was
Ffl was cut into four sides and used as a test piece, and subjected to an underwater release test Nα
The test was conducted according to 2. The results are shown in FIG. In FIG. 5, A corresponds to Example 2, B corresponds to Example 3, C corresponds to Example 4, D corresponds to Example 5, E corresponds to Example 6, and F corresponds to Example 7.

The results shown in FIG. 5 show that the release rate of the drug from the sustained release substrate can be controlled by changing the mixing ratio of polyvinyl acetate and polyvinylpyrrolidone.

[Example 8] 50 parts of polyvinyl acetate (Mw = 69,000) and
J hinirhiolJ l' 7 (Mw= 1,200
,000) was dissolved and mixed in 250 parts of methanol, and 4 parts of indomethacin dissolved in a small amount of methanol was mixed, and this was cast on the treated surface of polyethylene laminate paper that had been subjected to release treatment. Then, it was quickly dried into a film by using a dryer to obtain a sustained release preparation which was a film-like base material containing indomethacin and had a thickness of 600 μm.

Next, in Japanese Patent Application Laid-open No. 249472, a mouth bandage consisting of an integrated film-like adhesive and a flexible film-like support was manufactured using the raw materials shown below, and the back side of the flexible film-like support was The film-like base material having a thickness of 600 μm produced above was bonded together by thermocompression bonding to obtain a sustained release preparation with an oral bandage.

This was cut into 1 cm square pieces and used as test pieces, and a test was conducted according to the underwater release test Nα3 below. The result is the 6th
As shown in the figure. Incidentally, a side view of the obtained sustained release preparation with oral bandage is shown in FIG. 2 is a sustained release preparation, 2 is a film-like support layer, and 3 is a film-like adhesive layer.

Film-like adherent> Carboxyvinyl polymer 47 parts Polyvinyl acetate 50 parts Sodium citrate
3 parts film-like support> polyvinyl acetate 100 parts water release test No. 3 > 200- Add 100 In1 of distilled water kept at 37°C in a 200-corresponding Erlenmeyer flask with a stopper, and prepare a sustained release film with a film-like adherent. A sample of the preparation test piece whose film-like adherent surface was fixed to a phenol resin plate with double-sided adhesive tape was immersed with the sustained-release preparation side up, and the Erlenmeyer flask with a stopper was immersed in a constant temperature bath at 37°C. . After a certain period of time, indomethacin was extracted by adding ethyl acetate 40 to distilled water, and after removing the solvent, methanol was added and subjected to high performance liquid chromatography (
Quantification was performed using IMPLC) to obtain the release rate of indomethacin.

(If PLC conditions) Column: Lichrosorb RP-18 Mobile phase: CIhCN (70 parts by volume) /n, o (30
capacity part).

Detector: HPLC manufactured by Tosoh Corporation, UV-8000 Detection wavelength: 254 parts m Internal standard Nidiphenyl From the results shown in Figure 6 above, the release of indomethacin showed sustained release.

[Example 9] 4 parts of propranolol hydrochloride dissolved in a small amount of methanol was used instead of sulfur and lithium guaiazulene sulfonates. Other than that, the thickness was 200μ as in Example 1.
A film-like base material of m was obtained.

Next, thermocompression bonding was carried out at a temperature of 140° C. using a small thermocompression laminator using three of the obtained film-like substrates to obtain a sustained release preparation with a thickness of 600 μm. This was cut into 1 cm square pieces and used as test pieces, and a test was conducted according to the underwater release test Nα4 below. The results are shown in FIG.

Water release test No. 4> Distilled water kept at 37°C was placed in a 50In1 Erlenmeyer flask with a stopper, and one side of a test piece of a sustained release preparation was fixed to a phenol resin board with double-sided adhesive tape. was immersed with the sustained-release formulation side up, and the Erlenmeyer flask with a stopper was immersed in a constant temperature bath at 37°C. After a certain period of time, the distilled water was filtered with a membrane filter and quantitatively determined using HPLC to obtain the release rate of propranolol hydrochloride.

(HPLC conditions) Column: Lichrosorb RP-18 Mobile phase: C1hCN (45 parts by volume) /) 120 (5
5 volumes).

Ac0II (0.2 capacity part) Detector: Tosoh HPLC, UV-800
0 detection wavelength: 230 parts m From the results shown in FIG. 8 above, the release of indomethacin showed a sustained release property.

[Example 10] Instead of 4 parts of propranolol hydrochloride dissolved in a small amount of methanol, 5 parts of 1-menthol, 4 parts of spearmin I oil, and 5 parts of sucrose, which had been decomposed and mixed in a small amount of water-methanol mixed solvent, were used. Other than that, the thickness was 6 as in Example 9.
A sustained release preparation of 00 μm was obtained. The obtained sustained release preparation
C111 was cut into square test pieces, and an intraoral coolness evaluation test was conducted according to the following method.

<Test method for determining the coolness window in the oral cavity> A test piece was inserted into the maxillary anterior teeth of nine volunteers, and the coolness in the oral cavity was investigated 2 hours after insertion. The results are shown in Table 3 below.

(Left below) 1-" L-Ichimugi From the results in Table 3 above, the obtained sustained-release preparation gave a refreshing feeling to the oral cavity even 2 hours after the start of the test, so the sustained release of the fragrance was confirmed. It can be seen that it shows gender.

From the above results, it can be seen that the experimental product has less discomfort than the comparative product and has excellent sustained release properties.

[Brief explanation of the drawing]

Figures 1, 2, and 3 are relationship diagrams of the water release rate and time in the water release test of Food Red No. 102; Figure 4;
FIG. 5 is a diagram of the relationship between the release rate of sodium guaiazulene sulfonate in water and time, FIG. 6 is a diagram of the relationship between the release rate of indomethacin in water and time, and FIG. 7 is a side view of an example product of the present invention. FIG. 8 is a diagram showing the relationship between the release rate of propranolol hydrochloride in water and time. Patent Applicant Nitto Electric Industry Co., Ltd. Agent Patent Attorney 4 Yukihiko O 0 30 60 90 120 +50 i
80 Time (min,) 1 Mi 3 Fu Time (min, ) 2 4 animals; -1171M1023QtPH,t'f'('/,)〆I 1102 required question address fight ('/,)

Claims (1)

[Claims] (1) A sustained release preparation consisting of a film-like base material containing a medicinal ingredient, wherein the film-like base material is a vinyl pyrrolidone polymer having a weight average molecular weight of 50,000 to 1,800,000 and a weight average molecular weight of 50,000 to 1,800,000. Average molecular weight 25,000-500,
1. A sustained-release preparation characterized in that it is constituted by a homogeneous product of 0.000 vinyl acetate polymer.