JP5739725B2 - Edible jelly-like composition, jelly-like preparation and method for producing jelly-like preparation - Google Patents

Description

The present invention relates to an edible jelly-like composition gelled with a non-volatile organic solvent, a jelly-form preparation, and a method for producing the jelly-form preparation.

At present, naked tablets, coated tablets, capsules, powders, granules, liquids and the like are on the market as drugs to be administered orally. As preparations that disintegrate in the oral cavity and are absorbed in the digestive tract, orally disintegrating tablets and fast-dissolving oral film have already been put on the market. Dosage forms that improve the benefits of patients and caregivers taking such attention are drawing attention.
With the increase in the elderly population, there is an increase in the number of patients who have difficulty in eating and drinking, so-called difficulty in chewing and swallowing. According to the former Ministry of Health and Welfare (current Ministry of Health, Labor and Welfare) Silver Science research report reported by Masayasu Sugihara et al.
Against this background, in recent years, the development of jelly-form preparations containing pharmaceuticals has been promoted, and several types of products have already been sold in Japan.
However, all of these jelly-form preparations were a portion type that is taken with a spoon or the like, or a pillow package type that is pushed out of a bag and taken. In addition, the jelly-form preparation itself was not a type that dissolves in the oral cavity, but a type that diffuses easily by physical force during swallowing.

Further, for example, as a jelly type dosage form containing water, for example, a jelly preparation containing carrageenan, locust bean gum, polyacrylic acid or a partially neutralized product or salt thereof (Patent Document 1), jelly base and A pharmaceutical jelly composition comprising an alkali salt (Patent Document 2) and a pharmaceutical jelly composition (Patent Document 3) containing carrageenan, guar gum and polyacrylic acid or a partially neutralized product or salt thereof are disclosed.
However, these jelly-form preparations are those using a thermoreversible gelling agent at a high temperature (about 60-100 ° C.), or those using an irreversible gelling agent by crosslinking the gelling agent, The jelly-form preparation itself is not of the type that dissolves in the oral cavity, but of the type that diffuses easily by physical force during swallowing. In addition, these conventional jelly-form preparations require a high temperature at the time of preparation, or use a metal salt as a cross-linking agent. Therefore, a drug having a particularly poor thermal stability, a protein having a high interaction with the metal salt, When the peptide is contained, its stability may be a problem.

In addition, these conventional jelly-form preparations are all gelled with water, and further contain natural polysaccharides as gelling agents and saccharides as additives. Heat sterilization etc. became essential, and there was a problem that addition of preservatives was necessary. In addition, since it contains a large amount of water, there is a problem that it is difficult to administer to patients who need water restriction such as kidney disease and heart disease. Furthermore, water penetrates the packaging material from the composition. Due to volatilization, there is a problem that an expensive packaging material having high moisture permeability is required for storage stability.
In order to solve such problems, for example, preparations that gel with saliva in a dry film-like dosage form that does not contain water include, for example, a water-swellable gel-forming layer and a drug using a crosslinked carboxyvinyl polymer. The formulation (patent document 4) which has a content layer is disclosed.

However, such a film-shaped preparation requires a certain amount of saliva in order to dissolve or swell in the oral cavity using a water-soluble polymer. It may have taken. In addition, since it easily absorbs moisture, it has a drawback that it easily adheres to the oral mucosa and feels uncomfortable. In particular, in the case of an oral dissolution type film preparation, there is a correlation between the solubility and the thickness and size of the film, and as a result, it was difficult to contain a drug amount exceeding 100 mg. Regarding the production method, it is disclosed that such a film-shaped preparation is prepared by dissolving a water-soluble polymer using water as a solvent, dissolving the drug therein, and drying by heating. In the case of a drug that is sensitive to heat, there is a concern that the drug content may be reduced by heating. Further, when the drug is in a liquid state, there is a concern that the film-form preparation may be dissolved, so that it may be difficult to maintain a certain shape.

JP-A-9-187233 JP 2004-99558 A JP 2004-99559 A Japanese Patent No. 4267926

In view of the above situation, the present invention is an edible jelly-like composition that does not contain water but is easy to swallow and dissolves in the oral cavity, and the edible jelly-like composition It is an object to provide a jelly-form preparation using the product and a method for producing the jelly-form preparation.

As a result of intensive investigations to solve the above problems, the present inventors have used a gelling agent, preferably gelatin that gels at normal temperature to maintain the solid state and dissolves easily at body temperature. By gelling without using water with a non-volatile organic solvent compatible with the gelling agent, it is not necessary to consider sterilization in the manufacturing process, and also consider moisture permeability, which is a problem in storage stability. It was found that the edible jelly-like composition suitable for the administration of food and pharmaceuticals through the oral cavity and oral cavity including sublingual administration was found from the property characteristics, and the present invention was completed. .

That is, the present invention includes a gelling agent and a nonvolatile organic solvent compatible with the gelling agent, and the gelling agent is readily water-soluble gelatin, and is a nonvolatile organic solvent compatible with the gelling agent. Is glycerin and / or propylene glycol, and the readily water-soluble gelatin is gelatin that requires less than 1000 mL of water at 40 ° C. to dissolve 1 g of gelatin sample, dissolves at body temperature in the oral cavity, It is an edible jelly-like composition characterized by not containing .
Moreover, the edible jelly-like composition of the present invention is in the form of a sheet or a film, and preferably has a thickness of 30 to 5000 μm .
Also, the amount of the gelling agent is preferably 0.1 to 40 wt% based on the total weight of the composition.
Moreover, it is preferable that the compounding quantity of the said non-volatile organic solvent is 10 to 99 weight% on the basis of the total weight of a composition.

Moreover, this invention is a jelly-form preparation characterized by further including a drug in the edible jelly-form composition of this invention.
The present invention also includes a step of preparing a gelling agent solution by mixing a gelling agent, a nonvolatile organic solvent compatible with the gelling agent and a drug, and a step of dispensing or stretching the gelling agent solution. and, viewed including the step of solidifying by cooling or cooling, the gelling agent is readily water-soluble gelatin, non-volatile organic solvent compatible with the gelling agent is glycerine and / or propylene glycol, wherein Water-soluble gelatin is a gelatin that requires less than 1000 mL of water at 40 ° C. to dissolve a 1 g gelatin sample, and is a method for producing a jelly-like preparation characterized by dissolving at body temperature in the oral cavity. .
The present invention is described in detail below.

The present invention is an edible jelly-like composition that contains a gelling agent and a non-volatile organic solvent that is compatible with the gelling agent, and does not contain water.
The shape of the edible jelly-like composition of the present invention is not particularly limited, and the optimum shape varies depending on the jelly strength and intended use. For example, when it is used as a jelly-form preparation taken by a patient or a cared person, it is preferable that the edible jelly-form composition has sufficient strength to be self-supporting and is in the form of a tablet, film or sheet. In particular, from the viewpoint of solubility in the oral cavity, a film and a sheet-like shape are preferable, and in this case, the thickness is preferably 30 to 5000 μm. If the thickness is less than 30 μm, there is a possibility of a problem from the viewpoint of film strength and product handleability, and if it exceeds 5000 μm, there is a risk of feeling uncomfortable when administered into the oral cavity, particularly sublingually.

The size of the edible jelly composition of the present invention is not particularly limited when used as a sheet-shaped preparation, but the plane area is preferably in the range of 0.5 to 6.0 cm ² . If it is less than 0.5 cm ² , it may be difficult to handle when the preparation is picked and administered. If it exceeds 6.0 cm ² , it should be completely put into the oral cavity, especially when sublingually. There is a risk of not being able to.
The planar shape of the sheet-shaped preparation is not particularly limited, and examples thereof include an arbitrary shape such as a rectangle such as a rectangle and a square, a polygon such as a pentagon, a circle and an ellipse. The polygon referred to here includes not only a perfect polygon but also a shape having R at the corners.
If the patient cannot take the medicine by himself / herself and is administered by a healthcare worker or caregiver, the strength of the edible jelly-like composition should be softened, and cup packaging or pillow packaging that can be taken with a spoon etc. A shape is also desirable.

The said gelatinizer is a material used as the base material of the edible jelly-like composition of this invention.
The gelling agent is not particularly limited as long as it is edible and has gelling ability, but gelatin is preferably used. By including gelatin as a gelling agent, the edible jelly-like composition of the present invention can be gelled at room temperature and easily dissolved at body temperature in the oral cavity.
In the present specification, “edible” means that it can be administered orally and is pharmaceutically acceptable.

Gelatin can cause gelation at the lowest temperature among thermoreversible gelling agents, and manufactures a preparation using the edible jelly-like composition of the present invention at a temperature from room temperature to around 40 ° C. The stability at the time of manufacture of a drug with low thermal stability can be ensured. Among these gelatins, a grade called readily water-soluble gelatin is preferable.
As used herein, “easily water-soluble gelatin” means gelatin that requires less than 1000 mL of water at 40 ° C. in order to dissolve 1 g of a gelatin sample.
Gelatin usually has a triple helical structure in the molecular structure and is hardly water-soluble (poorly water-soluble gelatin). The readily water-soluble gelatin can be obtained by loosening the molecular structure of the poorly water-soluble gelatin to obtain a random coiled molecular structure.

The gelatin preferably has a property of not gelling at 32 ° C. and gelling at around 5 ° C. when formed into a 10% by weight aqueous solution. This is because gelatin having such properties is not readily water-soluble gelatin, but depending on the molecular weight and the hydroxyproline content in gelatin, there is a grade that can be used satisfactorily as the gelling agent.

Gelatin that can be used as the above-mentioned gelling agent is obtained by degrading and extracting proteins contained in animal skins and bones with enzymes, and those that are acid-treated or alkali-treated from pigs, cattle, and fish it can.
The gelatin can be prepared at normal temperature during production, and when the edible jelly-like composition of the present invention is used in a jelly-like preparation, from the viewpoint of stability during production of a heat-sensitive drug, fish or pig Derived gelatin is preferred. From this point of view, the gelatin may have a hydroxyproline content of 5.2 to 9.2 mol% in the amino acid composition as long as the average molecular weight exceeds 90,000. Examples of such gelatin include fish-derived gelatin, such as salmon-derived gelatin (hydroxyproline content in amino acid composition: 5.4 mol%), carp-derived gelatin (hydroxyproline content in amino acid composition: 7. 6 mol%) tilapia-derived gelatin (hydroxyproline content in amino acid composition: 8.0 mol%), and tilapia-derived gelatin is particularly preferable.

Here, the amino acid composition is obtained by analysis by hydrolyzing gelatin, separating by ion exchange chromatography, and detecting by ninhydrin.
In addition, as a specific example of the amount (mol%) of hydroxyproline in the amino acid composition obtained by the above method, for example, it is as follows.
Chicken: 10.8 mol%
Ostrich: 10.4 mol%
Mouse: 8.7 mol%
Pig: 9.4 mol%
Cattle: 9.5 mol%

The gelatin is preferably a gelatin having an average molecular weight of 50,000 to 90,000 regardless of the amount of hydroxyproline in the amino acid composition.
Here, “average molecular weight” in the present specification means a weight average molecular weight, and is measured by gel filtration chromatography analysis.
Furthermore, the average molecular weight here means not the molecular weight of the polypeptide chain trimer of gelatin but the molecular weight of each polypeptide chain monomer.

In the edible jelly-like composition of the present invention, the content of the gelling agent is preferably 2 to 40% by weight, more preferably 3.5 based on the total weight of the edible jelly-like composition of the present invention. -30% by weight, more preferably 5-10% by weight. If it is less than 2% by weight, gelation may not occur at room temperature. On the other hand, if it exceeds 40% by weight, solubility in the oral cavity becomes extremely slow, which may cause a problem in use.

The nonvolatile organic solvent that is compatible with the gelling agent has an action of assisting the dissolution of the edible jelly-like composition of the present invention. By controlling the content of the nonvolatile organic solvent in the edible jelly-like composition of the present invention, the dissolution time of the edible jelly-shaped composition of the present invention can be easily controlled. Therefore, the edible jelly-like composition of the present invention is suitable both when dissolved and taken in the oral cavity and when slowly dissolved in the oral cavity, particularly under the tongue, to release the drug.
Based on the total weight of the edible jelly-like composition of the present invention, the content of the nonvolatile organic solvent is preferably 10 to 99% by weight, more preferably 20 to 80% by weight. If it is less than 10% by weight, the solubility in the oral cavity becomes extremely poor, which may cause a problem in use. On the other hand, if it exceeds 99% by weight, storage of physical properties such as shape retention at room temperature is possible. There is a risk of poor stability.

The non-volatile organic solvent is not particularly limited as long as it is compatible with the gelling agent and is edible, but preferably a polyhydric alcohol having 2 to 4 OH groups in the molecule and having 4 or less carbon atoms. Used. When the number of OH groups in the polyhydric alcohol molecule is less than 2, compatibility with a gelling agent such as gelatin may be deteriorated. On the other hand, the number of OH groups in the polyhydric alcohol molecule may be four. When it exceeds, melting | fusing point will rise, it may become solid at normal temperature, and the use as a solvent may become difficult.
Moreover, when the carbon number of the polyhydric alcohol exceeds 4, compatibility with a gelling agent such as gelatin may be deteriorated.

As such a polyhydric alcohol, for example, at least one selected from the group consisting of glycerin, propylene glycol, and ethylene glycol is preferably exemplified.
Such nonvolatile organic solvents are used alone or in combination of two or more. Among these, glycerin and / or propylene glycol are preferred from the viewpoint of safety for administration to humans when contained in a large amount in the edible jelly-like composition of the present invention.

Moreover, the edible jelly-like composition of the present invention does not contain water.
Since the edible jelly-like composition of the present invention does not contain water, a general edible jelly-like composition does not require the addition of a necessary sterilization step or preservative, and has an advantage in terms of production cost. It is also suitable when applied to dietary supplements and pharmaceutical dosage forms for patients who need water restriction.
In the present specification, “not including water” includes a case where substantially no water is included. For example, the water content is 5% by weight based on the total weight of the edible jelly-like composition of the present invention. This means that it is preferably 2.5% by weight or less, more preferably 1% by weight or less.

The edible jelly-like composition of the present invention may contain an antifoaming agent.
Examples of the antifoaming agent include sorbitan fatty acid esters and sucrose fatty acid esters.
Examples of the sorbitan fatty acid ester include sorbitan monooleate, sorbitan trioleate, sorbitan sesquioleate, coconut oil fatty acid sorbitan, polyoxyethylene sorbitan fatty acid ester, and the like.
Examples of the sucrose fatty acid ester include sucrose stearate, sucrose oleate, sucrose palmitate, sucrose myristic ester, sucrose behenate, sucrose erucate, and sucrose. Examples include mixed fatty acid esters.

Moreover, the edible jelly-like composition of the present invention includes, as a component constituting the base material of the edible jelly-like composition, in addition to the above-mentioned substances, a fragrance, a flavoring agent, a sweetener, a colorant, an antiseptic, Agents, antioxidants, stabilizers, surfactants and the like may be used as appropriate.

The edible jelly-like composition of the present invention may contain additives that improve physical properties and solubility.
Examples of the additive include monosaccharides, disaccharides, tri-hexasaccharide sugars and sugar alcohols thereof as shown below.
Monosaccharides include, for example, aldotetroses such as erythrose and throse, aldose pentose such as ribose, lyxose, xylose and arabinose, allose, talose, gulose, glucose, altrose, mannose, galactose, idose, etc. Examples include keto tetroses such as roulose, ketopentoses such as xylulose and ribulose, ketohexoses such as psicose, fructose, sorbose and tagatose. Examples of the disaccharide include α-diglucoside such as trehalose, cordobiose, nigerose, maltose and isomaltose, β-diglucoside such as isotrehalose, sophorose, laminaribiose, cellobiose and gentiobiose, and α, β-diglucoside such as neotrehalose. In addition, lactose, sucrose, isomaltulose (palatinose) and the like can be mentioned. Examples of the trisaccharide include raffinose. Examples of trisaccharide to hexasaccharide oligosaccharides include fructo-oligosaccharides, galacto-oligosaccharides, xylo-oligosaccharides, isomalt-oligosaccharides, chitin-oligosaccharides, chitosan-oligosaccharides, oligo-glucosamines, dextrins, cyclodextrins, and the like. .

Examples of monosaccharide alcohols include tetritols such as erythritol, D-threitol, and L-threitol, pentitols such as D-arabinitol and xylitol, D-iditol, galactitol (dulcitol), and D-glucitol (sorbitol). Hexitol such as mannitol, cyclitol such as inositol, and the like. Examples of the disaccharide alcohol include maltitol, lactitol, and reduced palatinose (isomalt). Examples of the oligosaccharide alcohol include pentaerythritol and reduced maltose starch syrup.
In the edible jelly-like composition of the present invention, the sugar or sugar alcohol may be substituted, and one kind or a mixture of two or more kinds may be used.

From the viewpoint that the sheet-form preparation using the edible jelly-like composition of the present invention dissolves easily in the oral cavity and does not greatly change the viscosity of the solution in the production process, the sugar or sugar alcohol is a monosaccharide to Trisaccharides or these sugar alcohols are preferred.

The amount of such additives is preferably 1 to 80% by weight, more preferably 5 to 70% by weight, based on the total weight of the edible jelly-like composition of the present invention. If it is less than 1% by weight, there is a possibility that sufficient physical properties for use cannot be ensured. On the other hand, if it exceeds 80% by weight, the edible jelly-like composition of the present invention can be formed into a sheet or film shape by the added additive. When used as a preparation, it may be difficult to control physical properties.

The edible jelly-like composition of the present invention can provide a jelly-form preparation by containing a drug to obtain a pharmaceutical composition.
In the present specification, the drug means a substance having some physiological activity. A jelly-form preparation further comprising a drug in the edible jelly-form composition of the present invention is also one aspect of the present invention.

In the jelly-form preparation of the present invention, the drug is preferably a drug that can be administered to a mammal such as a human through its sublingual, oral, or intestinal tract, that is, orally administrable. Specific examples of such drugs include general anesthetics, hypnotics / sedatives, antiepileptics, antipyretic analgesic / anti-inflammatory drugs, antipruritics, neuropsychiatric drugs, central nervous system drugs, anti-dementia drugs, topical drugs Anesthetics, skeletal muscle relaxants, autonomic drugs, antispasmodics, antiparkinson drugs, antihistamines, cardiotonic drugs, arrhythmic drugs, diuretics, antihypertensive drugs, vasoconstrictors, coronary vasodilators, peripheral vasodilators Drugs, arteriosclerotic drugs, cardiovascular drugs, respiratory stimulants, antitussive expectorants, hormonal drugs, suppurative diseases topical drugs, analgesic / antipruritic / convergence / anti-inflammatory drugs, parasitic skin disease drugs, hemostatic drugs Examples include drugs for treating gout, drugs for diabetes, drugs for antineoplastic tumors, antibiotics, chemotherapeutic drugs, narcotics, smoking cessation aids, allergens for desensitization therapy, and vaccines.

The drug should also be present in the adhesive layer in an amount, also referred to herein as an effective amount, sufficient to produce a desired result in the treatment of a disease, condition or disorder, for example, the desired therapeutic result. Can do.
An effective amount of drug means, for example, an amount of the drug that is non-toxic but sufficient to produce a selected effect over a specified period of time. Such an amount can be readily determined by one skilled in the art.

The drug may be a solid drug or a liquid drug. The solid drug here means a drug that is solid at room temperature (25 ° C.), that is, a drug having a melting point higher than 25 ° C. The melting point here means a value measured by DSC, model number DSC6220 (manufactured by Seiko Instruments (SII)).
The liquid drug means a drug having fluidity at room temperature (25 ° C.), that is, a drug having a viscosity of 0.05 to 100,000 mPa · s. The viscosity of the drug is measured using an E-type viscometer while keeping the drug at 25 ° C.

The concentration of the drug is usually 1 × 10 ⁻¹⁰ to 80% by weight based on the total weight of the jelly-form preparation of the present invention, although it varies depending on the nature thereof. If it is less than 1 × 10 ⁻¹⁰ % by weight, it may not show efficacy in many drugs from the viewpoint of clinical effects. If it exceeds 80% by weight, the physical properties of the edible jelly-like composition will be significantly reduced and There may be a problem with the shape retention of the edible jelly-like composition.

The jelly-form preparation of the present invention includes, for example, a step of preparing a gelling agent solution by mixing a gelling agent, a nonvolatile organic solvent compatible with the gelling agent and a drug, and dispensing the gelling agent solution. Or it can manufacture by the method of including the process of extending | stretching and solidifying by standing_to_cool or cooling.
Such a method for producing the jelly-form preparation of the present invention is also one aspect of the present invention.
In the method for producing a jelly-form preparation of the present invention, the jelly-form composition of the present invention can be produced by not adding a drug.

In the step of preparing the gelling agent solution, first, a gelling agent such as readily water-soluble gelatin and other additives are dissolved in a predetermined amount of a non-volatile organic solvent by room temperature or heating, and the non-volatile organic solvent is dissolved in the non-volatile organic solvent. Additives that do not dissolve are uniformly dispersed.
When the drug is stable to heat, the drug is added together with the gelling agent and the like to prepare a gelling agent solution. On the other hand, in the case where the drug is unstable to heat, after dissolving the gelling agent and the like, the gel is cooled to room temperature to around 35 ° C., and then the heat-labile drug is added and mixed by stirring. An agent is prepared. Furthermore, you may add the said drug in the process of dispensing or extending | stretching the gelatinizer solution mentioned later.
Here, when foam is generated during the preparation of the gelling agent solution, the foam is sufficiently removed by standing for a long time or performing vacuum or vacuum degassing.

In the step of dispensing or stretching the gelling agent solution and the step of solidifying by cooling or cooling, a predetermined amount of the gelling agent solution is plastic or aluminum having a desired size at a temperature of 28 ° C to 32 ° C. Dispense into blister case and pillow packaging and cool and solidify immediately after dispensing. Instead of the dispensing method, an appropriate amount of the gelling agent solution may be spread on a plastic release film, cooled and solidified, and cut into a desired size.

In addition, when water is added to the gelling agent solution, it is necessary to perform heat drying or vacuum drying before cooling and solidifying in this step.
Moreover, when preparing content of the non-volatile organic solvent contained in the jelly-form preparation to manufacture, you may perform a cold-air drying process or a cooling pressure reduction drying process after this process.

The obtained sheet or film-like jelly-form preparation is preferably sealed and packaged as necessary to obtain a product.
The method for producing a jelly-form preparation of the present invention is very useful in that it can be prepared at a low temperature of 35 ° C. or lower, preferably 30 ° C. or lower, particularly for a thermally unstable drug.

The edible jelly-like composition of the present invention is a jelly-like composition that does not contain water. By using gelatin as a gelling agent, particularly easily water-soluble gelatin, it gels at room temperature and easily at body temperature in the oral cavity. It has the characteristic of dissolving in
Moreover, the edible jelly-like composition of the present invention can easily control the dissolution time by controlling the content of the nonvolatile organic solvent. From the viewpoint that this dissolution time can be controlled, it is possible to reduce the amount of sublingual sensitization as a pharmaceutical dosage form absorbed from the oral mucosa and sublingual mucosa that require residence time in the oral cavity, and to sensitize allergens from the sublingual mucosa. Suitable for sensitization therapy.
In addition, from the viewpoint of not containing water, the edible jelly-like composition of the present invention does not require the addition of a sterilization step or preservative, which is necessary for general jelly, and has an advantage in terms of production cost. It is also suitable as a dietary supplement and pharmaceutical dosage form for patients who need water restriction.
In the edible jelly-like composition of the present invention, gelatin and polyols such as glycerin and propylene glycol, which are generally known to improve storage stability of proteins and peptides, are preferably used. Is expected to be stable.
Of course, the edible jelly-like composition of the present invention may be swallowed as it is, or may be swallowed after being rapidly dissolved in the oral cavity. Furthermore, it is possible to expect the absorption from the oral mucosa and the sublingual mucosa by controlling the dissolution time in the oral cavity. The jelly-like preparation using the edible jelly-like composition of the present invention is suitable for patients with water restriction and swallowing from the viewpoint that there is no feeling of residue because it can be dissolved at all body temperatures and it does not contain water. It can greatly improve the QOL of difficult patients and caregivers.

The present invention will be specifically described by the following examples, but the present invention is not limited to these examples.

Example 1
To 9.5 parts by weight of propylene glycol (manufactured by Wako Pure Chemical Industries, Ltd.), 0.5 part by weight of readily fish-derived water-soluble gelatin (water-soluble gelatin CSF, manufactured by Nippi) is added and dissolved while stirring at a temperature of 60 ° C. I let you. After dissolution, 1 g each was dispensed into a 5 cm ² plastic blister case (Cryomold (square) No. 3, manufactured by Sakura Finetech Co., Ltd.) and cooled at 2-8 ° C. for one day to obtain an edible composition. .

(Examples 2 to 7)
According to the composition shown in Table 1, an edible composition was obtained in the same procedure as in Example 1.
In Examples 5 and 7, glycerin was used instead of propylene glycol (manufactured by Wako Pure Chemical Industries, Ltd.), and in Examples 6 and 7, fish-derived water-soluble gelatin (water-soluble gelatin CSF, manufactured by Nippi) was used instead. Porcine-derived water-soluble gelatin (water-soluble gelatin CS, manufactured by Nippi) was used.

(Comparative Example 1)
To 9.0 parts by weight of polyethylene glycol 400 (manufactured by Wako Pure Chemical Industries, Ltd.), 1.0 part by weight of readily fish-derived water-soluble gelatin (water-soluble gelatin CSF, manufactured by Nippi) was added and stirred at a temperature of 60 ° C. Since it did not dissolve, it was heated to 80 ° C. and stirred, but did not dissolve. 1 g of the solution in which the precipitate remains is dispensed into a 5 cm ² plastic blister case (Cryomold (square) No. 3, manufactured by Sakura Finetech Co., Ltd.), cooled at 2-8 ° C. for one day, and edible. A composition was obtained.

(Comparative Example 2)
To 9.0 parts by weight of polyethylene glycol 400 (manufactured by Wako Pure Chemical Industries, Ltd.), 1.0 part by weight of pork-derived water-soluble gelatin (water-soluble gelatin CS, manufactured by Nippi) was added and stirred at a temperature of 60 ° C. Since it did not dissolve, it was heated to 80 ° C. and stirred, but did not dissolve. 1 g of the solution in which the precipitate remains is dispensed into a 5 cm ² plastic blister case (Cryomold (square) No. 3, manufactured by Sakura Finetech Co., Ltd.), cooled at 2-8 ° C. for one day, and edible. A composition was obtained.

(Example 8)
5 parts by weight of easily derived gelatin derived from porcine water (water-soluble gelatin CS, manufactured by Nippi) was placed in 43.9 parts by weight of glycerin (manufactured by Wako Pure Chemical Industries, Ltd.), and heated to 60 ° C. to dissolve. In this solution, 50 parts by weight of precipitated calcium carbonate as a drug (manufactured by Bihoku Powder Chemical Co., Ltd.), 0.1 part by weight of sucralose (manufactured by Saneigen FFI Co., Ltd.), citric acid (Japanese Pharmacopoeia citric acid hydrate) (Manufactured by Komatsuya) 1.0 part by weight was added and mixed at 50 ° C. with stirring. After mixing, dispense 2.0 g each into a 5 cm ² plastic blister case (Cryomold (square) No. 3, manufactured by Sakura Finetech Co., Ltd.) and store it at 2-8 ° C. overnight. Obtained.

(Examples 9 and 10)
According to the composition shown in Table 2, a film-form preparation was obtained in the same procedure as in Example 8. Instead of precipitated calcium carbonate (manufactured by Bihoku Powder Chemical Co., Ltd.) as a drug, lanthanum carbonate hydrate (manufactured by Wako Pure Chemical Industries, Ltd.) was used in Example 9, and ethyl icosapentate (manufactured by Wako Pure Chemical Industries, Ltd.) was used in Example 10. ) Was used.

[Test method]
In Examples and Comparative Examples, when preparing edible compositions or film-form preparations (hereinafter collectively referred to as samples), whether or not various gelling agents dissolve (preparability), and jelly-like by cooling after preparation It was evaluated from three points, whether or not (gelability), whether or not separation of the nonvolatile organic solvent was observed after storage at 25 ° C. for 1 month (storage stability). The results are shown in Table 3.
Moreover, regarding Examples 1-7, in order to measure the dissolution characteristics in the oral cavity, a disintegration test was performed and the dissolution time was measured. The results are shown in Table 4.
Each test method is shown below.

(1) Possibility of preparation When each sample was prepared, it was evaluated whether each gelling agent was dissolved in a non-volatile organic solvent. The evaluation criteria are as follows.
3: Dissolved completely and became a clear solution.
2: Although it melt | dissolved, some turbidity was seen.
1: Some undissolved residue was seen.
0: hardly dissolved.

(2) Gelation property (jelly property)
At the time of preparing each sample, each solution was cooled at 2 to 8 ° C., and it was evaluated whether or not it became a jelly at that time. The evaluation criteria are as follows.
3: An edible jelly-like composition or jelly-like preparation that was elastic even when pressed with a finger and did not adhere a gelling agent to the finger.
2: Although it became an edible jelly-like composition or jelly-form preparation, it was soft and lacked elasticity.
1: An edible jelly-like composition or jelly-like preparation, but the gelling agent adhered to the finger.
0: No gelation with a viscous gelling agent.

(3) Storage stability test The sample prepared in the thermostat set to 25 degreeC was stored, and it took out one month after the start of storage, and evaluated the sensory test (tactile sensation). The evaluation method followed the sensory test (tactile feeling) evaluation method.
3: No separation of the non-volatile organic solvent (liquid component) was observed.
2: Some separation of the non-volatile organic solvent (liquid component) was observed on the surface of the sample.
1: The separation of the non-volatile organic solvent (liquid component) was observed on the surface of the sample.
0: Separation was severe and the gelling agent was immersed in a non-volatile organic solvent (liquid component).
In addition, (1) preparation possibility “0: hardly dissolved” sample and (2) gelation property “0: hardly dissolved” sample was scored as 0 without performing the test. .

(4) Oral dissolution time measurement The test was conducted according to the disintegration test method described in the 15th revision Japanese Pharmacopoeia. Distilled water was put into a 1000 mL low-profile beaker, and the test was conducted under the condition that the tester was moved up and down at a temperature of 37 ± 2 ° C. with 29 to 32 reciprocations per minute and an amplitude of 53 to 57 mm.
Put the edible composition according to Examples 1 to 7 in the tester, start the test under the conditions described above, and completely dissolve the edible composition according to Examples 1 to 7 from the start of the test. The time for disappearance from the tester was taken as the oral dissolution time.

As shown in Table 3, the samples according to the examples are good results in all evaluation items, are edible jelly-like compositions and jelly-like preparations that do not contain water, and include various gelling agents (water Even when blended with (easily soluble gelatin), good evaluation results were obtained, and even when various nonvolatile organic solvents (glycerin and propylene glycol) were used, good evaluation results were obtained.
On the other hand, the sample according to Comparative Example 1 had a poor gelling property (jelly forming property). Moreover, the sample which concerns on the comparative example 2 was a bad result in any evaluation item.

As shown in Table 4, the dissolution time in the oral cavity could be adjusted by controlling the content of the nonvolatile organic solvent contained in the edible jelly-like composition.

The edible jelly-like composition of the present invention is a jelly-like composition that does not contain water. By using gelatin as a gelling agent, particularly easily water-soluble gelatin, it gels at room temperature and easily at body temperature in the oral cavity. It has the characteristic of dissolving in
Moreover, the edible jelly-like composition of the present invention can easily control the dissolution time by controlling the content of the nonvolatile organic solvent. From the viewpoint that this dissolution time can be controlled, it is possible to reduce the amount of sublingual sensitization as a pharmaceutical dosage form absorbed from the oral mucosa and sublingual mucosa that require residence time in the oral cavity, and to sensitize allergens from the sublingual mucosa. Suitable for sensitization therapy.
In addition, from the viewpoint of not containing water, the edible jelly-like composition of the present invention does not require the addition of a sterilization step or preservative, which is necessary for general jelly, and has an advantage in terms of production cost. It is also suitable as a dietary supplement and pharmaceutical dosage form for patients who need water restriction.
In the edible jelly-like composition of the present invention, gelatin and polyols such as glycerin and propylene glycol, which are generally known to improve storage stability of proteins and peptides, are preferably used. Is expected to be stable.
Of course, the edible jelly-like composition of the present invention may be swallowed as it is, or may be swallowed after being rapidly dissolved in the oral cavity. Furthermore, it is possible to expect the absorption from the oral mucosa and the sublingual mucosa by controlling the dissolution time in the oral cavity. The jelly-like preparation using the edible jelly-like composition of the present invention is suitable for patients with water restriction and swallowing from the viewpoint that there is no feeling of residue because it can be dissolved at all body temperatures and it does not contain water. It can greatly improve the QOL of difficult patients and caregivers.

Claims (6)

A gelling agent and a non-volatile organic solvent that is compatible with the gelling agent,
The gelling agent is readily water-soluble gelatin, and the non-volatile organic solvent compatible with the gelling agent is glycerin and / or propylene glycol,
The readily water-soluble gelatin is gelatin that requires less than 1000 mL of water at 40 ° C. to dissolve a 1 g gelatin sample,
Dissolves at body temperature in the mouth,
An edible jelly-like composition characterized by not containing water. The edible jelly-like composition according to claim 1, which has a sheet-like or film-like shape and a thickness of 30 to 5000 µm. The edible jelly-like composition according to claim 1 or 2 , wherein the amount of the gelling agent is 0.1 to 40% by weight based on the total weight of the composition. The edible jelly-like composition according to claim 1, 2 or 3 , wherein the compounding amount of the nonvolatile organic solvent is 10 to 99% by weight based on the total weight of the composition. A jelly-form preparation, further comprising a drug in the edible jelly-form composition according to claim 1, 2, 3 or 4 . A step of preparing a gelling agent solution by mixing a gelling agent, a non-volatile organic solvent compatible with the gelling agent and a drug;
Dispensing or stretching the gelling agent solution; and
Look including the step of solidifying by cooling or cooling,
The gelling agent is readily water-soluble gelatin, and the non-volatile organic solvent compatible with the gelling agent is glycerin and / or propylene glycol,
The readily water-soluble gelatin is gelatin that requires less than 1000 mL of water at 40 ° C. to dissolve a 1 g gelatin sample,
A method for producing a jelly-form preparation, which dissolves at body temperature in the oral cavity .