JP2020094016A - Thermo-fusible transpiration agent - Google Patents

Abstract

To provide a thermo-fusible transpiration agent that prevents deterioration in dosage form and material from the production to the use by consumers.SOLUTION: A thermo-fusible transpiration agent contains (i) a polyethylene glycol of 55 mass% or more with a weight average molecular weight of 1800 or more, (ii) at least one nonionic surfactant, and (iii) an active ingredient.SELECTED DRAWING: None

Description

The present invention relates to a heat-melting vaporizing agent containing an active ingredient in a base material having a specific composition.

The heat-melting evaporation agent contains an active ingredient such as an aromatic component, a deodorant component, an insecticidal component, a repellent component, and a bactericidal component in a base material that is melted by heating, and when heated and melted, the active component evaporates into the environment. As a preparation and a heating and melting means, a method of putting it in a flame or a heating container and melting and evaporating it is known.

Conventionally, as a heat-melting and evaporating agent, a formulation containing an active ingredient in a base material containing wax as a main component is commercially available.
However, the heat-melting vaporizing agent may be exposed to a relatively harsh environment such as high temperature during the distribution process from the production to the use by the consumer. In some cases, the active ingredient with a high content was released, the original fragrance or activity was impaired, or it was deformed or discolored and could not be handled as a product.

On the other hand, for the purpose of releasing the fragrances having different volatility together, a volatile fragrance is added to the base material containing polyethylene glycol and/or hydrogenated castor oil having a weight average molecular weight of 4000 or more and optionally wax. A solid composition containing is proposed (Patent Document 1). However, in this document, the effect exerted by such a composition has not been verified, and its characteristics are unknown. Further, it is stated that the hardened castor oil is used to make it into a gel state. However, the heat-melting and vaporizing agent containing the hardened castor oil is likely to be deformed or discolored during the distribution process. In this respect, the heat-melting vaporizing agent of this document contains polyethylene glycol having a weight average molecular weight of 4000 or more. This high molecular weight polyethylene glycol is preferable from the viewpoint of stability of the vaporizing agent, but the heat-melting vaporizing agent containing this is However, the diffusibility of the active ingredient during heating is not always sufficient.

For the purpose of stabilizing the period from production to use, 0.1 to 20% of fragrance and 0.1 to 50% of polyethylene glycol having a weight average molecular weight of 5000 to 11000 of 40 to 95% are used. A heating and melting transpiration agent composed of particles containing starch granules is disclosed (Patent Document 2). Even in this document, the stability has not been verified and its actual characteristics are unknown, but starch granules are regarded as a component for imparting stability. However, if the heating-melting vaporizing agent containing starch granules is repeatedly heated and cooled during production or use, the starch granules are decomposed or deteriorated, so that the vaporizing agent deteriorates. Polyethylene glycol having a weight average molecular weight of 5,000 to 11,000 is preferable from the viewpoint of the stability of the vaporizing agent, but a heat-melting vaporizing agent containing the same does not necessarily have sufficient diffusibility of the active ingredient during heating.

JP, 2007-526343, A Japanese Patent Publication No. 2018-500087

The present invention, in the above-mentioned state of the art, does not cause the deterioration of the dosage form or the material from the production to the use by the consumer, and has an excellent diffusion property of the active ingredient, and to provide a heat-melting evaporation agent. To aim.

The present inventors, as a result of the investigation, found that the above problem can be solved by dispersing the active ingredient in a base material containing a specific molecular weight polyethylene glycol and a specific nonionic surfactant, The present invention has been completed.

That is, the present invention provides the following heat-melt evaporation agent, evaporation method, container for heat-melt evaporation apparatus, and heat-melt evaporation apparatus.
[1] (i) 55% by mass or more of polyethylene glycol having a weight average molecular weight of 1800 or more and less than 5000,
(ii) at least one nonionic surfactant,
(iii) A heat-melting transpiration agent containing an active ingredient.
[2] The heating according to [1], which contains at least one of polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene block copolymer, sorbitan fatty acid ester and polyethylene glycol fatty acid ester as the nonionic surfactant. Melt evaporation agent.
[3] The heat-melting evaporation agent according to [1] or [2], which further contains a porous carrier.
[4] A method of evaporating the active ingredient by heating and melting the vaporizing agent according to any one of [1] to [3].
[5] The method according to [4], wherein the evaporation agent is heated and melted by a heating and melting evaporation device equipped with a container made of silicon rubber or fluororubber.
[6] A container for a heat-melting evaporation device for putting the evaporation agent according to any one of [1] to [3] into the material for heating, melting, and evaporating, which is made of silicone rubber or fluororubber. Is a container.
[7] A heating and melting evaporation device, which comprises the evaporation agent according to any one of [1] to [3] and a container made of silicone rubber or fluororubber in which the evaporation agent is placed.

With the above composition, the heat-melting and vaporizing agent of the present invention is stable without deterioration of the qualities and dosage forms from the production to the use by the consumer, and is excellent in the diffusion property of the active ingredient.

FIG. 1 shows an example of an apparatus for heating and melting a vaporizing agent.

As described above, the heat-melting vaporizing agent of the present invention contains an active ingredient in a base material containing polyethylene glycol (hereinafter abbreviated as PEG) having a specific molecular weight and a specific nonionic surfactant.

The weight average molecular weight of PEG constituting the base material of the heat-melting and vaporizing agent of the present invention is 1800 or more and less than 5,000, preferably 3,000 or more and less than 5,000.
When the base material is made of PEG having a weight average molecular weight of less than 1800, when exposed to high temperature in the distribution process, deterioration of the quality of the agent such as discoloration and deterioration of the dosage form such as sagging may occur. If the weight average molecular weight is 5,000 or more, the diffusion property of the transpiration agent tends to be insufficient.
Here, the "weight average molecular weight" used in the specification of the present application means a value calculated from a hydroxyl value measured by the pyridine phthalic anhydride method according to JIS K-1557 6.4, and hereinafter, simply "molecular weight". That.

The heat-melting vaporizing agent of the present invention contains 55 mass% or more of PEG having a molecular weight of 1800 or more and less than 5000, preferably PEG having a molecular weight of 3000 or more and less than 5000, and preferably 60 to 90 mass%. Included, and more preferably 65 to 85% by mass. Even when the content of PEG having a molecular weight of 1800 or more and less than 5000 is less than 55% by mass, deterioration of the dosage form such as sagging may occur when exposed to high temperature during the distribution process. However, if a PEG having a molecular weight of 1800 or more and less than 5000 is contained in the above range, a PEG having a molecular weight outside this range, for example, a PEG having a molecular weight of 5000 or more may be contained.

The surfactant contained in the heat-melting vaporizing agent of the present invention may be any nonionic surfactant other than polyoxyethylene hydrogenated castor oil (hereinafter abbreviated as POE hydrogenated castor oil), and examples thereof include polyoxyethylene alkyl ether ( Hereinafter, abbreviated as POE alkyl ether), polyoxyethylene polyoxypropylene block copolymer (hereinafter abbreviated as POE/POP block copolymer), sorbitan fatty acid ester, polyethylene glycol fatty acid ester (hereinafter PEG fatty acid ester) Abbreviated), polyoxyethylene sorbitan fatty acid ester (hereinafter abbreviated as POE sorbitan fatty acid ester), and glycerin fatty acid ester, preferably POE alkyl ether, POE/POP block copolymer, and sorbitan fatty acid ester. At least one is included. These nonionic surfactants enhance the miscibility between the active ingredient and the above-mentioned PEG, and further enhance the stability of the dosage form of the heat-melting evaporation agent.

As the POE alkyl ether, from the above viewpoint, a POEC _12-18 alkyl ether having a repeating number of ethylene oxide units of 20 to 200 is preferable, and a POEC _12-15 alkyl ether having a repeating number of ethylene oxide units of 25 to 100 is more preferable. preferable.

The POE/POP block copolymer also preferably has a molecular weight of 800 to 40000 from the same point. The POE/POP molar ratio is preferably 0.1-10. The POE/POP block copolymer is particularly preferably a block polymer having a molecular weight of 3000 to 25000 and a POE/POP molar ratio of 0.8 to 6.

As the sorbitan fatty acid ester, sorbitan C _12-18 fatty acid ester is preferable. Preferred examples of the sorbitan fatty acid ester include sorbitan monooleate, sorbitan isostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate and sorbitan trioleate.

Examples of the PEG fatty acid ester include polyethylene glycol monostearate and the like. A PEG fatty acid ester having a POE addition mole number of 20 to 100 is preferable, and a PEG fatty acid ester of 25 to 80 is more preferable.
Examples of the POE sorbitan fatty acid ester include POE(20) sorbitan monostearate and POE(20) sorbitan tristearate, with POE(20) sorbitan tristearate being preferred.
Examples of the glycerin fatty acid ester include glycerin monooleate, glycerin monostearate and glycerin monopalmitate, and glycerin monostearate and glycerin monopalmitate are preferable.

In the transpiration agent of the present invention, among the above-mentioned nonionic surfactants, a POE/POP block copolymer is preferable, and it is preferable to include this alone or in combination with another nonionic surfactant in the transpiration agent. . The POE/POP block copolymer has an effect of particularly improving the miscibility of the active ingredient and PEG, and can uniformly disperse the active ingredient in the obtained transpiration agent.

The content of the nonionic surfactant in the transpiration agent of the present invention is preferably 1 to 35% by mass, more preferably 3 to 30% by mass.

The active ingredient contained in the transpiration agent of the present invention is not particularly limited, except that it is a substance that can be volatilized at the melting temperature of the base material, such as a fragrance, a deodorant, a repellent, an insecticide and a bactericide. Various active ingredients can be included, and it is also possible to combine two or more active ingredients, such as a combination of a fragrance and an insecticide or fungicide.

As the fragrance, for example, musk, ryunobu, abies oil, almond oil, page oil, perch oil, kaychi oil, citronella oil, eucalyptus oil, fennel oil, garlic oil, ginger oil, grapefruit oil, lemon oil, Natural flavors such as lemongrass oil, nutmeg oil, peppermint oil, orange oil, turpentine oil, sage oil, pinene, limonene, linalool, geraniol, citronellal, borneol, benzyl alcohol, anise alcohol, anethole, eugenol, aldehyde, citral, citronellal , Vanillin, carvone, ketone, menthone, acetophenone, coumarin, cineol, ethyl acetate, octyl acetate, butyl propionate, isopropyl isobutyrate, allyl caproate, ethyl benzoate, methyl cinnamate, artificial flavors such as methyl salicylate, etc. Be done. These fragrances can be used alone or in combination of two or more as a mixed fragrance.

Examples of the deodorant and/or deodorant include lauryl methacrylate, geranyl crotonate, acetophenone myristate, paramethylacetophenone benzaldehyde, benzyl acetate, benzyl propionate, amylcinnamic aldehyde, anisic aldehyde, diphenyl oxide, methyl benzoate. , Ethyl benzoate, methyl phenylacetate, ethyl phenylacetate, neoline, safrole, citronella oil, lemongrass oil and the like. These deodorant and/or deodorants can also be used alone or in combination of two or more.

The insecticides include, for example, natural pyrethrins, pyrethrin, allethrin, phthalthrin, resmethrin, furamethrin, permethrin, phenothrin, cyphenothrin, prallethrin, bifenthrin, Transfluthrin, metofluthrin, profluthrin, Mepafurutorin, dimefluthrin, imiprothrin, empenthrin, etofenprox , Pyrethroid insecticides such as silafluofen; Carbamate insecticides such as propoxur and carbaryl; Organophosphorus insecticides such as fenitrothion and DDVP; Oxadiazole insecticides such as metoxadiazone; Phenylpyrazole insecticides such as fipronil; Imidacloprid , Neonotetinoid insecticides such as dinotefuran; Sulfonamide insecticides such as amidoflumet; Pyrrole compounds such as chlorfenapyr; Insect juvenile hormone-like compounds such as methoprene and hydroprene; Antijuvenile hormone-like compounds such as plecosene; Molting hormone-like compounds such as ecdysone; inhibitors of chitin synthesis such as chlorfluazuron, diflubenzuron, hexaflumuron, buprofezin, essential oils such as phytoncide, light oil, orange oil, cinnamon oil, clove oil; isobornylthiocyano Acetate (IBTA), isobornyl thiocyanoethyl ether (IBTE), a quaternary ammonium salt, benzyl salicylate, etc. are mentioned, and these can be used individually by 1 type or in combination of 2 or more types. Among them, pyrethroid insecticides, carbamate insecticides, oxadiazole insecticides and sulfonamide insecticides are preferable because of their excellent volatility, and in particular, phenothrin, cifenotrin, permethrin, methoxadiazone, propoxur, amidoflumetho, etofenprox. , Transfluthrin, empentrin and metofluthrin are preferred.

Examples of the bactericidal agent and/or antifungal agent include Irgasan DP300, phenol compounds such as isopropylmethylphenol, Dausyl S-13, hinokitiol, Preventol A3, Preventol A4, thiabendazole, dioxin and the like. These agents can be used alone or in combination of two or more.

Insect repellents and repellents include, for example, diet, di-n-butyl succinate, hydroxyanisole, rotenone, ethyl-butylacetylaminopropionate, icaridin, 3-(Nn-butyl-N-acetyl)amino. Examples include propionic acid ethyl ester, P-menthane-3,8-diol, and the like. These can be used alone or in combination of two or more.

In a preferred embodiment of the present invention, the active ingredient may be supported on an organic or inorganic porous carrier and contained in the substrate. By supporting the active ingredient on the porous carrier, the release of the active ingredient is further suppressed even in a harsh environment in the distribution process, and the release of the active ingredient is continued for a longer period during use.
Examples of the porous carrier made of an inorganic material include silica, zeolite and alumina, and examples of the carrier made of an organic material include cyclodextrin. Of these, silica is preferable.

The transpiration agent of the present invention may contain any component as long as the effects of the present invention are exhibited, and for example, an evaporation aid, a disintegrant, an excipient, an antioxidant, a pigment or the like can be contained. ..
Examples of transpiration aids include zinc stearate, aluminum stearate, barium stearate, calcium stearate, zinc oxide, zinc carbonate, calcium carbonate, titanium dioxide, carbon black, antimony trioxide, decabromodiphenylene oxide, and trihydrate anhydrous. Mellitic acid, maleic anhydride, benzotriazole, 4,4′-oxybis(benzenesulfonylhydrazide), urea and the like can be mentioned. By using these in combination, the volatilization efficiency of the active ingredient can be adjusted.

Examples of the disintegrant include organic acid esters such as paraoxybenzoic acid ester, stearic acid ester, ethyl lactate and chlorophenyl salicylate; organic acids such as lactic acid, malic acid, fumaric acid, tartaric acid, adipic acid, succinic acid; phosphoric acid and the like. And the like. When the disintegrant is contained, the disintegration of the preparation by heating is promoted, and the volatilization efficiency of the active ingredient can be increased.

Examples of the excipient include sugars such as sucrose and glucose; sugar alcohols such as maltitol, sorbitol and xylitol.

Examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, vitamin E and its derivatives, catechin compounds, flavonoid compounds, and the like, and in particular, they are susceptible to oxidative action due to contact with air such as aromatic components. In the case of the active ingredient, it is preferable to include an antioxidant.

The vaporizing agent of the present invention is used by melting the base material by heating to volatilize the active ingredient. Therefore, the present invention also provides a method of heating and melting the above-mentioned evaporation agent to evaporate the active ingredient.

In the present invention, the method for heating and melting the evaporative agent is not particularly limited, but an apparatus for melting the evaporative agent in the container 2 by heat from the heating element 1 as shown in FIG. 1 is convenient. The temperature of the heating element itself may be appropriately set depending on the heat radiation state of the device as long as it satisfies the container temperature described later, but considering the heat resistance of the evaporation agent, an upper limit of about 200° C. is preferable, The upper limit is preferably about 180°C.
Further, as the material of the container 2, generally, an elastomer, a general-purpose heat-resistant resin such as polypropylene or polyethylene, a metal such as aluminum or stainless steel, or a ceramic product can be used.
When such a device is used, the transpiration agent is taken out from the container after use, and it is convenient if the mold release is easy at this time. From this point of view, it is preferable that the container is made of an elastomer material that is resistant to a temperature of at least 100° C. and is stretchable at room temperature. Examples of materials having such characteristics include nitrile rubber, silicone rubber, and fluororubber, which are relatively affordable to the former two, but in the case of a paraffin wax-based vaporizer, the vaporizer in the container is There is a problem that the components permeate and leave a residue during release. On the other hand, in the above-mentioned vaporizing agent of the present invention, even if a container formed of various elastomer materials such as nitrile rubber and silicon rubber is used, there is no problem that the components of the vaporizing agent penetrate into the container, and the vaporizing agent is separated cleanly. Can be typed.
Therefore, according to the present invention, by using the above-mentioned vaporizing agent in a heating and melting vaporizing apparatus provided with a container formed of an elastomeric material that is resistant to a temperature of at least 100° C. and can expand and contract at room temperature, the vaporizing agent can be easily prepared. It is possible to provide a method that enables easy mold release. Also provided is a solid formulation which achieves a simple release of the vaporizing agent and which is resistant to a temperature of at least 100° C. and contains the vaporizing agent described above in a container formed of an elastomeric material which is stretchable at room temperature.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

1. Preparation of Heating Melt Evaporating Agent First, the molecular weights are 1300 to 1600 (PEG1540, NOF CORPORATION), 1850 to 2150 (PEG2000, NOF CORPORATION), 3040 (PEG4000, NOF CORPORATION), and 8311 (PEG6000, respectively). (NOF CORPORATION) PEG and polyoxyethylene (45) monomethyl ether, polyoxyethylene (40) C _12-15 alkyl ether, sorbitan monopalmitate, polyoxyethylene (300) polyoxypropylene (55) block polymer , And polyoxyethylene (50) hydrogenated castor oil, and any one or two nonionic surfactants were melted by heating and mixed to prepare an admixture A).
In addition, a fragrance (oriental fragrance, manufactured by Takasago International Corporation) or transfluthrin (trade name: Biothrin, manufactured by Sumitomo Chemical Co., Ltd.) as an active ingredient, dihydroxytoluene (H-BHT, manufactured by Honshu Chemical Co., Ltd.) In addition, after confirming that it was dissolved, or without being dissolved in dihydroxytoluene, a mixture B was prepared with or without addition of amorphous silica (Carplex #80).
Finally, the mixture A and the mixture B were mixed to obtain a transpiration agent. The composition ratio of each component of each example and comparative example is as shown in the following table.

2. Stability evaluation 2-1. Sample Preparation Approximately 10 g of the vaporizing agent obtained in each Example and each Comparative Example was filled in a silicon cylindrical container (diameter 50 mm×depth 15 mm), and solidified by cooling was used as a sample.
2-2 Test Method Each sample was placed in a transparent pillow (GL-PET12/LLDPE50, 80 mm×80 mm, manufactured by Toppan Printing Co., Ltd.), and the stability of the drug substance and the stability of the dosage form were tested as follows.
Stability of the formulation The mixture was allowed to stand at 25°C for 5 days or at 40°C for 3 days, and the change in color of the sample was visually confirmed. The evaluation criteria are as follows.
○: Brown change No ×: Brown change
Dosage form stability It was left to stand at 50°C for 2 hours or at 55°C for 3 hours, and it was visually confirmed whether the shape of the preparation was changed. The formulation in which the shape was changed was marked as X, and the formulation in which the shape was maintained was marked as O.

4. Evaluation of Evaporation Properties with and without Porous Carrier Evaporation properties were tested using the evaporation agents of Examples 12 and 13 which differed only with or without amorphous silica. 10 g of the sample of each example was continuously heated at about 100° C. for 50 hours using the hot plate-like heat source device of FIG. 1, and then transferred to a closed space of 2.16 m ³ for 1.5 hours in the space. It heated and sensory-evaluated according to the following evaluation criteria. The overall evaluation was evaluated by the average value of 7 panelists.

As described above, even after heating for 50 hours, the transpiration agent of Example 13 in which the fragrance was supported on silica was maintained at a higher level than the transpiration agent of Example 12 in both fragrance quality and strength.

5. Comparison of Evaporation Characteristics by Difference in PEG Molecular Weight Evaporation characteristics were compared using the evaporating agent of Example 13 (PEG:MW3040) and the evaporating agent of Comparative Example 8 (PEG:MW8311) containing PEGs having different molecular weights. Using a hot plate-like heat source device, 10 g of each transpiration agent was heated so that each transpiration agent was at 100° C. for 0.75 hours from the start of energization in a closed space of 2.16 m ³ , and the sensory evaluation was performed in the same manner as in Table 5. Was performed (N=10).

As described above, the transpiration agent of Example 13 having a small PEG molecular weight was higher in both fragrance and strength than the transpiration agent of Comparative Example 8 because it was more soluble and had higher diffusivity.

Evaluation of Penetration of Evaporative Agent into Elastomeric Container Using the evaporative agent of Example 13, for containers made of various materials, the penetrability into the container, the ease of taking out the preparation and the repeated use resistance, and the use during heating The smell was evaluated. 1 g of the transpiration agent of Example 13 was placed in a container 2 made of various materials shown in Table 8 shown in FIG. 1 and heated at about 100° C. for 24 hours continuously using a hot plate-like heat source device, Upon cooling, the formulation was removed from the container. The odor caused by the material of the container was heated during heating, and after cooling after heating, the releasability of the preparation from the container, reusability, and penetration of the preparation into the back of the container were visually evaluated.

1. Heating element 2. container

Claims (7)

(i) 55% by mass or more of polyethylene glycol having a weight average molecular weight of 1800 or more,
(ii) at least one nonionic surfactant,
(iii) A heat-melting transpiration agent containing an active ingredient. The heat melting evaporation agent according to claim 1, comprising at least one of polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene block copolymer, sorbitan fatty acid ester, and polyethylene glycol fatty acid ester as the nonionic surfactant. . Furthermore, the heat-melting evaporation agent of Claim 1 or 2 containing a porous carrier. A method of evaporating the active ingredient by heating and melting the evaporative agent according to any one of claims 1 to 3. The method according to claim 4, wherein the evaporating agent is heated and melted by a heating and melting evaporation device provided with a container made of silicone rubber or fluororubber. A container for a heating-melting evaporation device for putting the evaporating agent according to any one of claims 1 to 3 and heating, melting, and evaporating, the container being made of silicone rubber or fluororubber. A heating and melting evaporation apparatus comprising the evaporation agent according to any one of claims 1 to 3 and a container made of silicone rubber or fluororubber in which the evaporation agent is placed.