JP2014227391A - Water-swellable laminate film and swallowable substance-coated body - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a water-swellable laminate film to be a gelatinous film having moderate strength by absorbing moisture, and a swallowable substance-coated body coated with a swallowable substance by using this water-swellable laminate film.SOLUTION: At least one face of a film (A) containing 8 to 35 mass% of a pharmaceutically acceptable carboxylate group-containing water-soluble polymer (a1) and 8 to 35 mass% of a pharmaceutically acceptable polyvalent metal compound (a2) having a solubility of 0.1 g/100 g or less in water at 25°C, where particles of the (a2) component are inside present in dispersion state, with a film (B) containing 50 to 95 mass% of a nonionic water-soluble polymer (b1) and 3 to 25 mass% of a pharmaceutically acceptable organic acid (b2) having a molecular weight of 1000 or less, to obtain a water-swellable laminate film. By using this water-swellable laminate film, a swallowable coated body is coated with a swallowable substance.

Description

  The present invention relates to a water-swellable laminated film that absorbs moisture and becomes a gel-like film having an appropriate strength, and to a swallowed article covering a swallowed article using this water-swellable laminated film.

In recent years, research and development of film-form preparations containing active ingredients such as pharmaceuticals have been actively conducted. For example, Patent Documents 1 and 2 disclose film-form preparations that rapidly disintegrate or dissolve in the oral cavity and can be taken without water.
However, in these film-form preparations, since the film dissolves in the oral cavity in a short time, a part of the active ingredient adheres to the oral cavity and the esophagus, and the necessary amount of the active ingredient is not in the target body. There was a case where it was not reliably transported to this part.

Patent Documents 3 and 4 disclose a film-form oral administration agent that has a water-swellable gel-forming layer as the outermost layer, and a swallow is covered with the water-swellable gel-forming layer.
However, when such a water-swellable gel-forming layer has low wet strength (strength in a swollen state by absorbing water), such an orally administered agent has a swallowed product in which the gel layer is broken and contained. There was a risk of being released into the oral cavity.

JP 11-116469 A JP 2004-043450 A WO2002 / 087622 pamphlet JP 2005-289868 A

  The present invention has been made in view of the above-described conventional technology, and a water-swellable laminated film that absorbs moisture and becomes a gel-like film having an appropriate strength, and swallowing using the water-swellable laminated film An object of the present invention is to provide a swallowed article covering body.

  As a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention contain a predetermined amount of a carboxylate group-containing water-soluble polymer and a specific polyvalent metal compound, and particles of the polyvalent metal compound are dispersed in the inside. A laminated film obtained by laminating a film containing a predetermined amount of a nonionic water-soluble polymer and a specific organic acid on at least one surface of an existing film is a gel-like film having an appropriate strength by absorbing moisture. By forming a film and covering the swallow using this laminated film, it is possible to obtain a swallow cover that is excellent in swallowability and sufficiently masked the bitterness and smell of the swallow The headline and the present invention were completed.

Thus, according to the present invention, the following water-swellable laminated films (1) to (13) and swallowed article coverings (14) and (15) are provided.
(1) Pharmaceutically acceptable carboxylate group-containing water-soluble polymer (a1) 8 to 35% by mass and a pharmaceutically acceptable polyvalent metal compound having a solubility in water at 25 ° C. of 0.1 g / 100 g or less The nonionic water-soluble polymer (b1) 50- is contained on at least one surface of the film (A) containing (a2) 8 to 35% by mass and in which particles of the component (a2) are present in a dispersed state. A water-swellable laminated film obtained by laminating 95% by mass and a film (B) containing 3 to 25% by mass of a pharmaceutically acceptable organic acid (b2) having a molecular weight of 1000 or less.
(2) The water-swellable laminated film according to (1), wherein the component (a1) is at least one selected from the group consisting of a sodium salt, a potassium salt, and an ammonium salt of a carboxyl group-containing polymer.
(3) The water swellability according to (2), wherein the carboxyl group-containing polymer is at least one selected from the group consisting of alginic acid, carboxymethylcellulose, gellan gum, xanthan gum, heparin, hyaluronic acid, pectinic acid and polyacrylic acid. Laminated film.
(4) The water-swellable laminated film according to any one of (1) to (3), wherein the 1 mass% aqueous solution of the component (a1) has a viscosity at 25 ° C. of 30 to 400 mPa · s.
(5) The water-swellable laminated film according to any one of (1) to (4), wherein the component (a2) is a calcium salt of an organic acid or an inorganic acid.
(6) The water-swellable laminated film according to any one of (1) to (5), wherein the particles of the component (a2) have an average particle size of 10 μm or less.
(7) The water-swellable laminated film according to any one of (1) to (6), wherein the film (A) further contains a nonionic water-soluble polymer (a3).
(8) The water-swellable laminated film according to any one of (1) to (7), wherein the film (A) further contains a plasticizer (a4).
(9) The water-swellable laminated film according to any one of (1) to (8), wherein the component (b1) is hydroxyalkyl cellulose.
(10) The water-swellable laminated film according to any one of (1) to (9), wherein the acid dissociation constant (pKa) of the component (b2) is 2 to 4.
(11) The component (b2) is at least one selected from the group consisting of citric acid, succinic acid, maleic acid, fumaric acid, lactic acid, malic acid, tartaric acid and gluconic acid. The water-swellable laminated film according to any one of the above.
(12) The water-swellable laminated film according to any one of (1) to (11), wherein the film (B) further contains a plasticizer (b3).
(13) The water-swellable laminated film according to any one of (1) to (12), obtained by laminating the film (B) on both surfaces of the film (A).
(14) A swallowed article covering body in which the swallowable article (c1) is covered with the water-swellable laminated film according to any one of (1) to (13).
(15) The swallow article covering according to (14), wherein the component (c1) is a pharmaceutically active ingredient.

According to the present invention, there are provided a water-swellable laminated film that absorbs moisture and becomes a gel-like film having an appropriate strength, and a swallowed article covering body that uses this water-swellable laminated film to coat a swallowed article. The
Since the water-swellable laminated film of the present invention has excellent wet strength, it is useful as a material for forming a swallowed article covering.
Since the swallowed article covering body of the present invention is a thing in which the swallowing object is coated with the water-swellable laminated film of the present invention, it is excellent in swallowing property, and the bitterness, smell, etc. of the swallowing substance are sufficiently masked. Yes, it can be taken without discomfort.

It is sectional drawing of the water-swellable laminated film of this invention. It is sectional drawing of the swallowing thing covering body of this invention. It is process sectional drawing showing the manufacturing process of the swallowing thing covering body of this invention.

  Hereinafter, the present invention will be described in detail by dividing into 1) a water-swellable laminated film and 2) a swallowed article covering.

1) Water-swellable laminated film The water-swellable laminated film of the present invention has a pharmaceutically acceptable carboxylate group-containing water-soluble polymer (a1) of 8 to 35% by mass and a solubility in water at 25 ° C. of 0.1 g. Of the pharmaceutically acceptable polyvalent metal compound (a2) in an amount of 8 to 35% by mass or less, and the particles of the component (a2) are present in a dispersed state inside the film. A film (B) containing 50 to 95% by mass of a nonionic water-soluble polymer (b1) and 3 to 25% by mass of a pharmaceutically acceptable organic acid (b2) having a molecular weight of 1000 or less on at least one surface ).

In the present specification, a pharmaceutically acceptable water-soluble polymer (a1) containing a carboxylate group, a pharmaceutically acceptable polyvalent metal compound (a2) having a solubility in water at 25 ° C. of 0.1 g / 100 g or less. , A nonionic water-soluble polymer (b1), and a pharmaceutically acceptable organic acid (b2) having a molecular weight of 1000 or less, respectively, (a1) component, (a2) component, (b1) component, (b2) component There are times.
“Pharmaceutically acceptable” means having no significant side effects or toxicity when administered to the human body.
The “water-soluble polymer” refers to a polymer having a viscosity of 10 mPa · s or more at 25 ° C. in a 1% by mass aqueous solution.

In the water-swellable laminated film of the present invention, in the film state before absorbing water, the component (a2) is present dispersed in the particle state in the film (A). Therefore, the component (a2) does not substantially react with the component (a1). The water-swellable laminated film of the present invention is excellent in storage stability over a long period of time.
And when this water-swellable laminated film absorbs moisture, the (b1) component in the film (B) dissolves and at the same time the (b2) component in the film (B) diffuses and the (a2 in the film (A) ) Promotes ionization of components. As a result, the released polyvalent metal ions interact with the carboxylate group of the component (a1), and an ionic bridge is constructed.
The water-swellable laminated film of the present invention is a gel-like film having an appropriate strength through such a process when moisture is absorbed.

[Film (A)]
The film (A) contains the component (a1) 8 to 35% by mass and the component (a2) 8 to 35% by mass, and the particles of the component (a2) are present in a dispersed state inside the film. .
“Present in a dispersed state” means that the component (a2) is present in the form of fine particles in the film (A).

The component (a1) is a pharmaceutically acceptable water-soluble polymer containing a carboxylate group.
By using the component (a1), a composition for forming a film (A) having excellent coating workability can be obtained. And since the water-swellable laminated film of this invention uses the film (A) containing (a1) component, it will be excellent in water-swellability and wet strength.

As the component (a1), sodium salt, potassium salt and ammonium salt of a carboxyl group-containing polymer are preferable. Here, examples of the carboxyl group-containing polymer include at least one selected from the group consisting of alginic acid, carboxymethylcellulose, gellan gum, xanthan gum, heparin, hyaluronic acid, pectinic acid and polyacrylic acid.
Among these, a sodium salt of a carboxyl group-containing polymer is preferable and a sodium salt of alginic acid is particularly preferable because a water-swellable laminated film having excellent wet strength can be easily obtained.
(A1) A component can be used individually by 1 type or in combination of 2 or more types.

The solubility of the component (a1) in water can be adjusted by selecting an appropriate cation. It can also be performed by controlling the molecular weight or the content of the carboxylate group.
The component (a1) preferably has a 1 mass% aqueous solution having a viscosity at 25 ° C. of 30 to 400 mPa · s, more preferably 45 to 350 mPa · s. By being in this range, it becomes easy to obtain a water-swellable laminated film that is superior in wet strength and swallowability.

  (A1) Content of a component is 8-35 mass% with respect to the whole film (A), Preferably it is 10-30 mass%. When the content of the component (a1) is too small, the resulting water-swellable laminated film tends to be inferior in wet strength, and when the content of the component (a1) is too large, the water-swellable laminated film is inferior in swallowability. Tend.

The component (a2) is a pharmaceutically acceptable polyvalent metal compound having a solubility in water at 25 ° C. of 0.1 g / 100 g or less.
Since the water-swellable laminated film of the present invention uses the film (A) containing the component (a2), it is excellent in swelling property and wet strength.

The solubility of the component (a2) in water at 25 ° C. is 0.1 g / 100 g or less, preferably 0.05 g / 100 g or less. When the solubility in water at 25 ° C. is 0.1 g / 100 g or less, the film (A) in which particles of the component (a2) are present in a dispersed state can be efficiently formed.
The lower limit of the solubility in water at 25 ° C. is not particularly limited, but is usually 0.0001 g / 100 g or more.

Examples of the component (a2) include magnesium salts, aluminum salts, calcium salts, iron salts, copper salts, and zinc salts of organic acids or inorganic acids. Examples of the organic acid include citric acid and acetic acid, and examples of the inorganic acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and carbonic acid.
Among these, a calcium salt of an organic acid or an inorganic acid is preferable because a water-swellable laminated film having excellent wet strength can be easily obtained.

Examples of calcium salts of organic acids or inorganic acids include calcium salts of organic acids such as calcium citrate; calcium salts of inorganic acids such as calcium phosphate and calcium carbonate. Among these calcium salts, calcium carbonate is particularly preferable because the particles can be easily dispersed in the film (A).
(A2) A component can be used individually by 1 type or in combination of 2 or more types.

  The component (a2) is a particulate material. The average particle diameter is usually 10 μm or less, preferably 1 to 10 μm. (A2) The average particle diameter of the component particles can be measured by an air permeation method.

  (A2) Content of a component is 8-35 mass% with respect to the whole film (A), Preferably it is 10-30 mass%. If the content of the component (a2) is too small, the resulting water-swellable laminated film tends to be inferior in wet strength. On the other hand, when there is too much content of (a2) component, there exists a tendency for the coating workability | operativity of a composition for film (A) formation to be largely inferior, and there exists a possibility that it may become difficult to obtain a film (A).

The film (A) may be referred to as a nonionic water-soluble polymer (a3) [hereinafter referred to as component (a3). ] May be contained.
The component (a3) is an electrically neutral water-soluble polymer that does not have a cationic group or an anionic group.
The film (A) contains the component (a3), so that the strength in the film state is improved. Moreover, the water-swellable laminated film using this film (A) is superior in swallowability.

  The component (a3) preferably has a 5 mass% aqueous solution having a viscosity at 37 ° C. of 1,000 to 100,000 mPa · s. When the viscosity is in the above range, a water-swellable laminated film excellent in strength and swallowability in a film state can be easily obtained.

Specific examples of the component (a3) include polyvinyl alcohol; polyvinyl pyrrolidone; hydroxyalkyl cellulose such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, and hydroxyethylcellulose; These can be used individually by 1 type or in combination of 2 or more types.
Among these, as the component (a3), hydroxyalkyl cellulose is preferable, and hydroxypropyl cellulose is more preferable.

  When the film (A) contains the component (a3), the content of the component (a3) is preferably 84% by mass or less, more preferably 1 to 80% by mass, and still more preferably based on the entire film (A). It is 10-70 mass%.

The film (A) may be referred to as a plasticizer (a4) [hereinafter referred to as (a4) component. ] May be contained.
By containing the component (a4), the film (A) is more excellent in flexibility and heat sealability.

  As the component (a4), a known plasticizer that can be used as a food additive can be used. Specific examples include glycerin, polyethylene glycol, triethyl citrate, propylene glycol, polyoxyethylene / polyoxypropylene glycol, triacetylene, sorbitol, glycerin triacetate, diethyl phthalate and lauric acid, and sucrose. These can be used individually by 1 type or in combination of 2 or more types.

  When the film (A) contains the component (a4), the content of the component (a4) is preferably 30% by mass or less, more preferably 0.1 to 30% by mass with respect to the entire film (A). .

Moreover, the film (A) may contain other additives. Other additives include sweeteners such as saccharin sodium, aspartame, acesulfame potassium, and sucralose; fragrances; colorants such as titanium oxide and various dyes; preservatives such as methyl hydroxybenzoate and propyl hydroxybenzoate; .
When the film (A) contains other additives, the content thereof is preferably 30% by mass or less, more preferably 0.1 to 30% by mass with respect to the entire film (A).

  The film (A) can be obtained, for example, as a film with a holding substrate (A) by applying the composition for forming a film (A) on the holding substrate and drying the obtained coating film. . This holding substrate can be peeled and removed at a predetermined stage such as before or after the production of the water-swellable laminated film.

  The composition for forming the film (A) is obtained by dispersing the component (a2) in an appropriate solvent, wherein the component (a1) is optionally mixed with the component (a3), the component (a4), and other additives. Can be prepared by adding and mixing.

Examples of the solvent used include protic polar solvents such as water and ethanol. These solvents can be used alone or in combination of two or more.
Especially, since the particle | grains of (a2) component can be efficiently disperse | distributed inside a film (A), the mixed solvent of water or water and ethanol is preferable.

The holding substrate to be used is not particularly limited as long as it can support the film (A). For example, plastic films such as polyethylene terephthalate film, polyethylene naphthalate film, polyethylene film, polypropylene film; papers such as glassine paper, clay coated paper, polyethylene laminated paper; and these films are treated with a silicone-based release agent. And so on.
The thickness of the holding substrate used is usually 5 to 200 μm, preferably 25 to 100 μm.

  Examples of the method for applying the film (A) forming composition on the holding substrate include a method of applying using a known coating apparatus such as a roll coater, a die coater, a gravure coater, and an applicator.

The temperature which dries the coating film of the composition for film (A) formation is 50-120 degreeC normally, Preferably it is 60-110 degreeC.
The drying time is usually several tens of seconds to several minutes.

The basis weight of the film (A) is not particularly limited, usually 10 to 400 g / ^{m 2,} preferably from 20 to 300 g / ^{m 2.}

[Film (B)]
The film (B) is a film containing (b1) component 50 to 95% by mass and (b2) component 3 to 25% by mass.

The component (b1) is an electrically neutral water-soluble polymer that does not contain a cationic group or an anionic group.
The component (b1) is a component that plays a role of maintaining the shape of the film (B).
Since the water-swellable laminated film of the present invention uses the film (B) containing the component (b1), the component (b2) is efficiently diffused when moisture is absorbed, and gelation takes place in a short time. It is a progression.
Specific examples of the component (b1) include the same ones as described above as the component (a3).

  (B1) Content of a component is 50-95 mass% with respect to the whole film (B), Preferably it is 60-90 mass%. When the content of the component (b1) is too small, the film (B) tends to be inferior in strength, and when the content of the component (b1) is too large, the resulting water-swellable laminated film is composed of the component (b2). Since the content is relatively lowered, the water swellability tends to be inferior.

The component (b2) is a pharmaceutically acceptable organic acid having a molecular weight of 1000 or less.
Since the water-swellable laminated film of the present invention uses the film (B) containing the component (b2), the component (a2) is efficiently ionized by the component (b2) when moisture is absorbed. Gelation proceeds efficiently in a short time.

(B2) The molecular weight of a component is 1000 or less, Preferably it is 60-1000, More preferably, it is 80-500. When the molecular weight is within the above range, the component (b2) can be diffused more efficiently in the film (A) when the water-swellable laminated film absorbs moisture.
The acid dissociation constant (pKa) of the component (b2) is preferably 2-4. When the acid dissociation constant is within this range, ionization of the component (a2) is further promoted.

Examples of the component (b2) include citric acid, succinic acid, maleic acid, fumaric acid, lactic acid, malic acid, tartaric acid, and gluconic acid.
These can be used individually by 1 type or in combination of 2 or more types.

  (B2) Content of a component is 3-25 mass% with respect to the whole film (B), Preferably it is 3-15 mass%. When the component (b2) is too small, the resulting water-swellable laminated film tends to be inferior in water swellability, and when the component (b1) is too large, the film (B) tends to be inferior in strength.

The film (B) may be referred to as a plasticizer (b3) [hereinafter referred to as (b3) component. ] May be contained.
A film (B) becomes a thing excellent by a softness | flexibility and heat-sealability by containing the (b3) component.

  Specific examples of the component (b3) include the same ones as described above as the component (a4).

  When the film (B) contains the component (b3), the content of the component (b3) is preferably 30% by mass or less, more preferably 0.1 to 30% by mass with respect to the entire film (B). .

Moreover, the film (B) may contain other additives. Examples of other additives include the same ones as described above as the additives for the film (A).
When the film (B) contains other additives, the content thereof is preferably 30% by mass or less, more preferably 0.1 to 30% by mass with respect to the entire film (B).

  The film (B) can be obtained, for example, as a film with a holding substrate (B) by applying a composition for forming a film (B) on a holding substrate and drying the obtained coating film. . This holding substrate can be peeled and removed at a predetermined stage such as before or after the production of the water-swellable laminated film.

  The composition for forming the film (B) is prepared by adding (b1) component, (b2) component, and (b3) component and other additives, if necessary, to an appropriate solvent and mixing them. Can do.

Examples of the solvent and holding substrate to be used include the same as those shown as the solvent and holding substrate for the film (A) forming composition.
Examples of the method for coating the film (B) forming composition on the holding substrate and the drying conditions for the obtained coating film include the same as those shown as the method for forming the film (A).

The basis weight of the film (B) is not particularly limited, usually 10 to 400 g / ^{m 2,} preferably from 20 to 300 g / ^{m 2.}

[Water-swellable laminated film]
A cross-sectional view of the water-swellable laminated film of the present invention is shown in FIG.
The water-swellable laminated film [1a] shown in FIG. 1 (a) is obtained by laminating the film (B) [3] on one surface of the film (A) [2].
The water-swellable laminated film [1b] shown in FIG. 1 (b) is obtained by laminating a film (B) [3a] and a film (B) [3b] on both sides of the film (A) [2]. It is obtained. At this time, the two films (B) may be the same or different.
Since the water-swellable laminated film of the present invention is superior in water swellability and wet strength, the film (B) is laminated on both sides of the film (A) like the water-swellable laminated film [1b]. What is obtained is preferable.
In addition, the water-swellable laminated film of the present invention is provided with holding substrates [4a] and [4b] used at the time of manufacturing the film (A) and film (B) as shown in FIG. There may be.

  In the water-swellable laminated film of the present invention, for example, a film with a holding substrate (A) and a film with a holding substrate (B) are overlapped so that the film (A) and the film (B) face each other. By heat sealing, it can be obtained as a water-swellable laminated film with a holding substrate. The holding substrates of both outermost layers can be peeled and removed at a predetermined stage.

  The heat sealing conditions are not particularly limited, but are usually 60 to 150 ° C., preferably 80 to 130 ° C., pressure 0.05 to 1 MPa, time 0.5 seconds to several seconds. By heat-sealing under such conditions, a water-swellable laminated film that is easily and firmly sealed can be obtained in a short time.

  The water-swellable laminated film of the present invention becomes a gel-like film having an appropriate strength by absorbing moisture, and covers (encapsulates or encloses) swallows such as pharmaceutically active ingredients, as will be described later. It is useful as an edible film.

2) Swallow thing covering body The swallow thing covering body of this invention coat | covers the swallow thing (c1) using the water-swellable laminated | multilayer film of this invention.

  The swallowed product (c1) is not particularly limited as long as it is an edible substance. For example, various pharmaceutically active ingredients; health foods such as vitamins, minerals, fibers, yeasts and supplements;

Specific examples of swallows (c1) include minor tranquilizers such as alprazolam, fludiazepam, and lorazepam; sleeping agents such as zolpidem tartrate; antiparkinson agents such as cavelcholine and methixene hydrochloride; therapeutic agents for Alzheimer type dementia such as donepezil hydrochloride; colchicine Therapeutic agents for gout such as: Clenbuterol hydrochloride, salbutamol sulfate, fenoterol hydrobromide, procaterol hydrochloride and the like bronchodilators; peptic ulcers such as rabeprazole Na, famotidine and lafutidine; antidiabetic agents such as voglibose; Antiarrhythmic agents such as bufetrol hydrochloride; antihypertensive agents such as enalapril maleate, quinapril hydrochloride, cilazapril, nifedipine, felodipine and benidipine hydrochloride; hyperlipidemic agents such as simvastatin; Vitamin preparations such as loxocobalamin; immunosuppressive agents such as tacrolimus hydrate; atopic skin treatment agents; hormone agents such as ethinylestradiol and methylestrenolone; migraine treatment agents such as lomerizine hydrochloride; antidepressants such as ifenprodil tartrate Antitussives such as loperamide hydrochloride; laxatives such as picosulfate Na; antiemetics such as azasetron hydrochloride, granisetron hydrochloride, ramosetron hydrochloride; mequitazine, homochlorcyclidine hydrochloride, chlor maleate; Antihistamines such as phenylamine; antiallergic agents such as cetirizine hydrochloride and emedastine fumarate; opium alkaloid-type analgesic and antitussives such as ethylmorphine hydrochloride and morphine hydrochloride; bactericides such as cetylpyridinium chloride; vitamins;
These may be used in combination of two or more kinds within a pharmaceutically acceptable range.

The shape of the swallowed product (c1) is not particularly limited, and examples thereof include a film shape, a tablet shape, a capsule shape, a powder shape, and a viscous body shape.
When the swallow (c1) is in the form of a film, the basis weight is not particularly limited, but is usually 10 to 400 g / m ² , preferably 20 to 300 g / m ² .
The swallow (c1) may contain a water-soluble polymer, a plasticizer, an additive and the like similar to the components of the water-swellable laminated film.

The layer structure of the swallowed article covering of the present invention can be appropriately determined in consideration of the gelation speed, gel strength, convenience, and the like.
A cross-sectional view of the swallow covering of the present invention is shown in FIG.
The swallowed article coverings [5a] to [5d] in FIGS. 2 (a) to (d) are obtained by coating the swallowed article (c1) [6] using two water-swellable laminated films. The swallowed article covering [5e] in FIG. 2 (e) is obtained by covering the swallowed article (c1) [6] with one water-swellable laminated film.

The swallowed article covering [5a] sandwiches the swallowed article (c1) [6], and the layer [3b] derived from the film B of the water-swellable laminated film [1b ′] and the water-swellable laminated film [1b ″] The layer [3c] derived from the film B is overlapped so as to face each other, and both are heat-sealed to cover the swallow (c1) [6].
The swallowed article covering [5b] sandwiched the swallowed article (c1) [6], and the layer [3a] derived from the film B of the water-swellable laminated film [1a ′] and the water-swellable laminated film [1a ″] The swallow (c1) [6] is coated by overlapping the film A-derived layer [3b] so as to face each other and heat-sealing the two.
The swallowed article covering [5c] sandwiches the swallowed article (c1) [6], and the water-swellable laminated film [1a ′]-derived layer [2a] and the water-swellable laminated film [1a ″] The swallow (c1) [6] is coated by overlapping the film A-derived layer [2b] so as to face each other and heat-sealing them.
The swallowed article covering [5d] sandwiches the swallowed article (c1) [6], and the water-swellable laminated film [1a ']-derived layer [2a] and the water-swellable laminated film [1a "] The layer [3b] derived from the film B is overlapped so as to face each other, and both are heat-sealed to coat the swallow (c1) [6].
The swallowed article covering [5e] encloses the swallowed article (c1) [6], bends it so that the layer [3b] derived from the film B faces each other, and heat-seal the layers [3b] derived from the film B. It is a thing.

  Among these, since it is excellent in swallowing property and masking properties such as bitterness and smell of swallowed material, the swallowed material cover [5a] or swallowed material cover [5e] obtained by using the water-swellable laminated film having a three-layer structure ] Is preferable.

Process sectional drawing which manufactures the swallow thing covering | covering bodies [5a] and [5e] is shown in FIG.
As shown in FIG. 3 (a), the swallowed article covering [5a] sandwiches the swallowed article (c1) [6] between two water-swellable laminated films [1b ′] and [1b ″] These two water-swellable laminated films [1b ′] and [1b ″] can be obtained by heat sealing.
The heat sealing is not particularly limited, but is usually performed at a temperature of 60 to 150 ° C., preferably 80 to 130 ° C., a pressure of 0.05 to 1 MPa, and a time of 0.5 seconds to several seconds.

  As shown in FIG. 3 (b), the swallowed article covering body [5e] is placed on one water-swellable laminated film [1b ′], and the swallowed article (c1) [6] is placed on the water-swellable laminated film [5e]. 1b ′] is folded in two, and the end portion is heat-sealed in the same manner as described above.

  Moreover, in these manufacturing processes, you may use the water-swellable film which formed the recessed part which can accommodate a swallowing thing (c1). By using the water-swellable film in which the concave portions are formed in advance, even when the swallow (c1) is relatively thick, the target swallow cover can be efficiently formed. Moreover, in this case, since heat sealing only needs to be performed on the peripheral edge of the recess, the heat history for the swallow (c1) can be further reduced.

  There is no restriction | limiting in particular as a method of forming a recessed part in a water-swellable film, A well-known press processing method can be utilized. For example, a method of embossing (processing for forming a concave portion on the surface of a sheet by a method such as embossing) using an embossing roll can be mentioned. This method is preferable from the viewpoint of work efficiency.

  What is necessary is just to determine the magnitude | size and shape of a recessed part according to the quantity and shape of a swallowing thing (c1). Usually, it has a cylindrical shape and a turret shape with a diameter of 2 to 20 mmφ, preferably 5 to 10 mmφ, and a depth of 0.5 to 8 mm, preferably 1 to 5 mm.

  The size and shape of the swallow article covering of the present invention are not particularly limited. When manufacturing, it may be manufactured from the beginning to have a size suitable for one swallow, or after heat sealing using a large water-swellable film, the size suitable for one swallow It may be cut into individual pieces.

  The swallowed article covering body of the present invention is excellent in swallowability and is sufficiently masked with the bitterness and smell of the swallowed article and can be taken without discomfort.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples.
Unless otherwise indicated, the part and% in each example are based on mass.

The materials used in Examples and Comparative Examples are shown below.
ALG1: Sodium alginate (viscosity of 1% aqueous solution at 25 ° C .: 45 mPa · s)
ALG2: sodium alginate (viscosity of 1% aqueous solution at 25 ° C .: 150 mPa · s)
ALG3: sodium alginate (viscosity of 1% aqueous solution at 25 ° C .: 350 mPa · s)
ALG4: Alginic acid (insoluble in water)
PAA1: polyacrylic acid PM1: calcium carbonate (average particle size: 2.5 μm, solubility in water at 25 ° C .: 0.02 g / 100 g)
PM2: calcium carbonate (average particle size: 5 μm, solubility in water at 25 ° C .: 0.02 g / 100 g)
PM3: calcium carbonate (average particle size: 8 μm, solubility in water at 25 ° C .: 0.02 g / 100 g)
PM4: calcium chloride (average particle size: 5 μm, solubility in water at 25 ° C .: 74.5 g / 100 g)
PM5: potassium alum (average particle size: 5 μm, solubility in water at 25 ° C .: 6.74 g / 100 g)
WSP1: hydroxypropyl cellulose (weight average molecular weight: 130,000)
WSP2: hydroxypropyl cellulose (weight average molecular weight: 60,000)
WSP3: hydroxypropylcellulose (weight average molecular weight: 325,000)
OA1: citric acid (acid dissociation constant pKa: 2.87)
OA2: malic acid (acid dissociation constant pKa: 3.24)
OA3: Gluconic acid (acid dissociation constant pKa: 3.86)
・ GLY: Glycerin

The viscosity at 25 ° C. of a 1% by mass aqueous solution was measured according to JIS K7117-1 4.1 (Brookfield rotary viscometer).
The average particle size was measured by an air permeation method.
The solubility in water was calculated by putting a sample in water, shaking it at 25 ± 5 ° C. every 5 minutes for 30 seconds, and determining the amount dissolved within 30 minutes.

[Example 1]
(I) Production of film with holding substrate (A) A predetermined amount of the materials shown in Table 1 was sequentially added to purified water, and the whole volume was stirred at 25 ° C. for 60 minutes to obtain a film having a solid content of 10% ( A) A composition 1 for formation was obtained.
Using the applicator, the film (A) -forming composition 1 was held so that the basis weight after drying was 40 g / m ² [polyethylene terephthalate film (trade name “SP-PET 381031”, manufactured by Lintec Corporation) )] Spread applied on top. Thereafter, the coating film was dried at 100 ° C. for 5 minutes to obtain a film with a holding substrate (A).
In addition, when the obtained film (A) with a holding base material was cut and the cross section was observed with an electron microscope, the particles of the polyvalent metal compound (a2) had the original particle size in the film (A). It was confirmed that they existed in a dispersed state.

(Ii) Production of film with retaining substrate (B) Predetermined amounts of the materials listed in Table 2 were sequentially added to purified water, and the whole volume was stirred at 25 ° C. for 60 minutes to obtain a film having a solid content of 10% ( B) A composition 1 for formation was obtained.
Using a applicator, the film (B) -forming composition 1 is held so that the basis weight after drying is 20 g / m ² [polyethylene terephthalate film (trade name “SP-PET 381031”, manufactured by Lintec Corporation) )] Spread applied on top. Thereafter, the coating film was dried at 100 ° C. for 5 minutes to obtain a film with a holding substrate (B).

(Iii) Production of water-swellable laminated film 1 One film (A) with a holding substrate and two films (B) with a holding substrate are prepared, and the holding substrate of the film with a holding substrate (A) is prepared. Was removed. Next, these films are laminated so as to have a layer structure of holding substrate / film (B) / film (A) / film (B) / holding substrate, temperature 110 ° C., pressure 0.15 MPa, time Heat sealing was performed for 1 second. Next, the holding substrates on both sides were peeled and removed to obtain a water-swellable laminated film 1.

(Iv) Production of swallowed article covering 1 Prepare two sheets of water-swellable laminated film 1 obtained by the above method, and press the one water-swellable laminated film 1 to obtain a diameter of 8 mmφ and a depth. A 3 mm recess was formed, and 10 mg of granules containing vitamin C and vitamin B2 as active ingredients were placed in the recess. The other water-swellable laminated film 1 is overlaid thereon, and the water-swellable laminated films 1 at the peripheral edge of the recesses are bonded together by heat-sealing for 1 second at a temperature of 120 ° C. and a pressure of 0.5 MPa. did.
Subsequently, the swallow thing covering body 1 by which the active ingredient was enclosed was cut | judged to the circular shape of diameter 15mm so that a recessed part may come to the center.

[Examples 2 to 15, Comparative Examples 1 to 9]
The composition for film (A) formation and the composition for film (B) formation were each prepared by the mixing | blending of Tables 1-3. Subsequently, using these, a film with a holding substrate (A) and a film with a holding substrate (B) were produced in the same manner as in Example 1.
By using the obtained film (A) with holding substrate and film (B) with holding substrate, a water-swellable laminated film with holding substrate and a swallowed covering were obtained in the same manner as in Example 1. .

In Comparative Examples 1, 2, and 9, since the film (A) forming composition was gelled, it could not be applied and the film (A) could not be produced.
In Comparative Example 4, the component (a2) in the composition for forming a film (A) was stagnant and could not be applied, and the film (A) could not be produced.
In Comparative Example 8, the component (a1) in the composition for forming a film (A) was damped and could not be applied, and the film (A) could not be produced.

About the swallow thing covering body obtained by the Example and the comparative example, the wet intensity | strength and swallowing property were evaluated on the following references | standards. The results are shown in Tables 1-3.
[Wet strength evaluation]
After gargleing and cleaning the oral cavity, the swallow coverings of each Example and Comparative Example were taken without water so that they were intentionally scraped with the upper jaw and tongue. Then, the presence or absence of the collapse of the swallowing covering was confirmed.
The swallowed material covering did not dissolve or disintegrate, the film shape was maintained for 1 minute or more, and the swallowed material covering dissolved or disintegrated by swallowing before being swallowed. The case was set as “x”.

[Swallowing evaluation]
In the above-described wet strength evaluation, after 20 seconds, swallowing is sufficient because swollen enough and easy to swallow. “△” indicates that sometimes the throat is clogged; did.

The following are understood from Tables 1-3.
The swallow cover of Examples 1 to 15 has sufficient wet strength and is excellent in swallowability.
On the other hand, in Comparative Examples 1, 2, 4, 8, and 9, the film (A) could not be produced.
In Comparative Example 3, since the content of the component (a2) is too small, the wet strength and swallowability are inferior.
In Comparative Example 5, since the content of the component (a1) is too small, the wet strength and swallowability are inferior.
In comparative example 6, since there is too much content of the (a1) component, it is inferior to swallowability.
In Comparative Example 7, since the content of the component (b2) is too small, the wet strength and swallowability are inferior.

1a, 1a ', 1a ", 1b, 1b', 1b", 1c ... Water-swellable laminated film 2, 2a, 2b ... film (A)
3, 3a, 3b, 3c, 3d ... Film (B)
4a, 4b ... holding substrate 5a, 5b, 5c, 5d, 5e ... swallowing thing covering body 6 ... swallowing thing (c1)

Claims (15)

A pharmaceutically acceptable polyvalent metal compound (a2) having a pharmaceutically acceptable carboxylate group-containing water-soluble polymer (a1) of 8 to 35% by mass and a water solubility at 25 ° C. of 0.1 g / 100 g or less. ) 8 to 35% by mass, and on the at least one surface of the film (A) in which the particles of the component (a2) are present in a dispersed state,
A film (B) containing 50 to 95% by mass of a nonionic water-soluble polymer (b1) and 3 to 25% by mass of a pharmaceutically acceptable organic acid (b2) having a molecular weight of 1000 or less is laminated. The resulting water-swellable laminated film.   The water-swellable laminated film according to claim 1, wherein the component (a1) is at least one selected from the group consisting of a sodium salt, a potassium salt, and an ammonium salt of a carboxyl group-containing polymer.   The water-swellable laminated film according to claim 2, wherein the carboxyl group-containing polymer is at least one selected from the group consisting of alginic acid, carboxymethylcellulose, gellan gum, xanthan gum, heparin, hyaluronic acid, pectinic acid and polyacrylic acid.   The water-swellable laminated film according to any one of claims 1 to 3, wherein the 1 mass% aqueous solution of the component (a1) has a viscosity at 25 ° C of 30 to 400 mPa · s.   The water-swellable laminated film according to any one of claims 1 to 4, wherein the component (a2) is a calcium salt of an organic acid or an inorganic acid.   The water-swellable laminated film according to any one of claims 1 to 5, wherein the particles of the component (a2) have an average particle diameter of 10 µm or less.   The water-swellable laminated film according to any one of claims 1 to 6, wherein the film (A) further contains a nonionic water-soluble polymer (a3).   The water-swellable laminated film according to any one of claims 1 to 7, wherein the film (A) further contains a plasticizer (a4).   The water-swellable laminated film according to any one of claims 1 to 8, wherein the component (b1) is hydroxyalkyl cellulose.   The water-swellable laminated film according to any one of claims 1 to 9, wherein the acid dissociation constant (pKa) of the component (b2) is 2 to 4.   The component (b2) is at least one selected from the group consisting of citric acid, succinic acid, maleic acid, fumaric acid, lactic acid, malic acid, tartaric acid and gluconic acid. Water-swellable laminated film.   The water-swellable laminated film according to any one of claims 1 to 11, wherein the film (B) further contains a plasticizer (b3).   The water-swellable laminated film according to any one of claims 1 to 12, obtained by laminating the film (B) on both surfaces of the film (A).   The swallow thing covering body which coat | covered the swallow thing (c1) using the water-swellable laminated | multilayer film in any one of Claims 1-13.   The swallowing covering according to claim 14, wherein the component (c1) is a pharmaceutically active ingredient.

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