WO2019017295A1

WO2019017295A1 - Gelled composition

Info

Publication number: WO2019017295A1
Application number: PCT/JP2018/026517
Authority: WO
Inventors: 坂西裕一; 山中基資; 中野万敬
Original assignee: 株式会社ダイセル; 名古屋市
Priority date: 2017-07-21
Filing date: 2018-07-13
Publication date: 2019-01-24
Also published as: JP6878724B2; JPWO2019017295A1

Abstract

Provided is a gelled composition containing a fluorinated compound at a high concentration. This gelled composition includes a miscible article. The miscible article is: a compound (A) represented by formula (a) (in the formula: R1 represents a monovalent hydrocarbon group or a monovalent group in which 2 or more hydrocarbon groups are bonded together via a linking group, and at least 30% of the hydrogen atoms bonded to the carbon atoms constituting R1 are substituted by at least one halogen atom such as a fluorine atom; X represents a halogen atom, a hydrogen atom, a nitrogen atom, or a hydroxy group; and n represents an integer of 1 to 3); and a compound (B) represented by formula (b) (in the formula: m1 and m2 are the same or different from each other, and represent an integer of 3 to 22; and Y represents a hydrogen atom or a hydroxy group). 75-99.9 wt% of the total amount of the constituents of the miscible article is derived from compound (A).

Description

Gel composition

The present invention relates to a gel-like composition containing a fluorinated compound in a high concentration. The gel composition is used in the fields of medicines, quasi drugs, cosmetics and the like. Priority is claimed on Japanese Patent Application No. 201-142253, filed on July 21, 2017, the content of which is incorporated herein by reference.

Fluorinated compounds such as fluorocarbons are extremely chemically and biologically inert and have high solubility of gas (eg, oxygen, carbon dioxide, air). For example, under an oxygen atmosphere at 37 ° C., the fluorocarbon can dissolve about 50% of its volume of oxygen. In addition, fluorinated compounds can transport and diffuse gases far away. Thus, fluorinated compounds are of interest as a means for delivering high concentrations of therapeutic gases to tissues and organs.

Patent Document 1 describes that when treating a wound such as a burn, the wound is brought into direct contact with a liquid fluorocarbon, or a bandage, a gauze or the like is brought into contact with a fluorocarbon. However, there was a problem in terms of usability.

And as a method of improving usability, it is conceivable to appropriately thicken a fluorinated compound such as fluorocarbon. It is known to use surfactants to thicken fluorinated compounds such as fluorocarbons.

Patent Document 2 describes that a gel is obtained by combining a fluorocarbon and a surfactant, separating a fluorocarbon phase concentrated by centrifugation or the like, and redispersing the fluorocarbon phase in an aqueous medium. There is. However, no gel containing fluorocarbon at a concentration of more than 50% by weight was obtained. In addition, complicated work was also a problem.

U.S. Pat. No. 4,366,169 Japanese Patent Application Laid-Open No. 63-100928

Accordingly, an object of the present invention is to provide a gel-like composition containing a fluorinated compound in a high concentration.
Another object of the present invention is to provide a gel-like composition which can be conveniently prepared and which contains a fluorinated compound in a high concentration.

The inventors of the present invention conducted intensive studies to solve the above problems, and as a result, a compatible substance obtained by compatibilizing a fluorinated compound with a fluorinated surfactant represented by the following formula (b) has high viscosity. Having high fluidity, being excellent in stability, being extremely chemically and biologically inert, and capable of maintaining high viscosity even when subjected to heat sterilization treatment, and the like; Since it contains in high concentration, it discovered that it was especially excellent in gas solubility or gas permeability. The present invention has been completed based on these findings.

That is, the present invention provides a gel-like composition comprising the following compatibilizer.
Compatibilizer: the following formula (a)

(Wherein, R ¹ represents a monovalent hydrocarbon group or a monovalent group in which two or more hydrocarbon groups are linked via a linking group, and a hydrogen atom of a hydrogen atom bonded to a carbon atom constituting R ¹ 30% or more is substituted by a halogen atom containing at least one fluorine atom, X is a halogen atom, a hydrogen atom, a nitrogen atom, or a hydroxyl group, and n is an integer of 1 to 3)
And a compound (A) represented by the following formula (b)

(Wherein, m1 and m2 are the same or different and each represents an integer of 3 to 22. Y represents a hydrogen atom or a hydroxyl group)
Compatibilized with the compound (B), wherein 75 to 99.9% by weight of the total of the compatibilizer components is a component derived from the compound (A)

The present invention also provides that the compound (A) is a perfluoroalkane, a perfluorocycloalkane, a perfluoroether, a perfluoropolyether, a perfluoroamine, and at least one of the fluorine atoms possessed by these compounds is a fluorine atom. The gel-like composition as described above, which is a compound substituted with at least one selected from a halogen atom, a hydrogen atom, and a hydroxyl group, and having at least one fluorine atom. Provide the goods.

The present invention also provides the gel-like composition as described above, which is a medicine, quasi-drug, cosmetics, or lubricant.

The present invention also provides the gel composition, which is a film forming agent.

The gel composition of the present invention has high viscosity and no flowability. In addition, the gel composition of the present invention is excellent in stability and extremely inactive chemically and biologically. Furthermore, the solubility and permeability of gas (for example, oxygen, carbon dioxide, air) are excellent. Furthermore, the gel composition of the present invention is stable to heat, and can maintain its viscosity high even after heat sterilization and the like.
Therefore, the gel composition of the present invention can be suitably used as a medicine, quasi-drug, cosmetics, lubricant, etc., and an external preparation applied topically to skin, mucous membrane, etc. (for example, pharmaceuticals) , Quasi-drugs, cosmetics, etc.). The gel composition of the present invention can also be suitably used as a film forming agent.

[Gel-like composition]
The gel composition of the present invention contains the following compatibilizer.
Compatibilized substance: a compatible substance of at least one compound (A) represented by the formula (a) and at least one compound (B) represented by the formula (b) Compatible material in which 75 to 99.9% by weight of the total amount of constituents of the product is a component derived from the compound (A)

(Compound (A))
The compound (A) in the present invention is a compound represented by the following formula (a), and is an oil component.

(Wherein, R ¹ represents a monovalent hydrocarbon group or a monovalent group in which two or more hydrocarbon groups are linked via a linking group, and a hydrogen atom of a hydrogen atom bonded to a carbon atom constituting R ¹ 30% or more is substituted by a halogen atom containing at least one fluorine atom, X is a halogen atom, a hydrogen atom, a nitrogen atom, or a hydroxyl group, and n is an integer of 1 to 3)

The hydrocarbon group includes an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, and a group to which these are bonded. In the present invention, among them, an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, or a group obtained by combining these is preferable.

Therefore, as the monovalent hydrocarbon group for R ¹ , a monovalent aliphatic hydrocarbon group, a monovalent alicyclic hydrocarbon group, and a monovalent group to which these are bonded are preferable.

The monovalent aliphatic hydrocarbon group is preferably an aliphatic hydrocarbon group having 1 to 20 carbon atoms (= C _1-20 ), and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group and an isobutyl group. Carbon number of 1 to 20 (preferably 1 to 10, particularly preferably 1 to 3), such as s-butyl, t-butyl, pentyl, hexyl, decyl, lauryl, myristyl and stearyl groups Alkyl groups; alkenyl groups having 2 to 20 carbon atoms such as vinyl, allyl, 1-butenyl, oleyl and linoleyl; and alkynyls having 2 to 20 carbons such as ethynyl and propynyl. be able to.

As the monovalent alicyclic hydrocarbon group, a C _3-20 alicyclic hydrocarbon group is preferable, and for example, a 3- to 20-membered member such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or a cyclooctyl group 3 to 15 membered, particularly preferably 5 to 8 membered cycloalkyl group; 3 to 20 membered (preferably 3 to 15 membered, particularly preferably 5 to 8 membered) such as cyclopentenyl group and cyclohexenyl group And the like) perhydronaphthalen-1-yl group, perhydrofluoranthren-3-yl group, perfluorodecalin-1-yl group, perfluoroperhydrophenanthren-1-yl group, norbornyl group, Adamantyl group, tricyclo [5.2.1.0 ^2,6 ] decan-8-yl group, tetracyclo [4.4.0.1 ^2,5 . Examples thereof include bridged cyclic hydrocarbon groups such as a [1, ^{7 10} ] dodecane-3-yl group.

Examples of monovalent hydrocarbon groups in which an aliphatic hydrocarbon group and an alicyclic hydrocarbon group are bonded include cycloalkyl substituted alkyl groups such as a cyclopentylmethyl group, a cyclohexylmethyl group and a 2-cyclohexylethyl group (for example, C _{3 -20} cycloalkyl substituted C _1-4 alkyl group etc.) and the like.

Among the monovalent hydrocarbon groups of R ¹ , monovalent saturated aliphatic hydrocarbon groups, monovalent saturated alicyclic hydrocarbon groups, and monovalent radicals having these combined are particularly preferable.

As a linking group, for example, a carbonyl group (-CO-), an ether bond (-O-), a thioether bond (-S-), an ester bond (-COO-), an amide bond (-CONH-), a carbonate bond ( -OCOO-) etc. can be mentioned.

As a halogen atom, in addition to a fluorine atom, a chlorine atom, a bromine atom and an iodine atom are included.

30% or more of the hydrogen atoms bonded to the monovalent hydrocarbon group or the monovalent group bonded to two or more hydrocarbon groups via a linking group are substituted with a halogen atom containing at least one fluorine atom Among them, it is preferable that at least 50% (particularly preferably at least 80%, particularly preferably at least 90%) is substituted by at least one halogen atom containing fluorine atom. The upper limit is 100%.

N is an integer of 1 to 3, and when X is a halogen atom, a hydrogen atom or a hydroxyl group, preferably n = 1. In addition, when X is a nitrogen atom, preferably n is 2 or 3.

Specific examples of the compound (A) include perfluoroalkanes (including linear and branched perfluoroalkanes), perfluorocycloalkanes (including monocyclic and polycyclic perfluorocycloalkanes), per Fluoroether, perfluoropolyether, perfluoroamine, and derivatives thereof (= at least one of the fluorine atoms of these compounds is substituted by at least one selected from a halogen atom other than a fluorine atom, a hydrogen atom, and a hydroxyl group Compounds having at least one fluorine atom) and the like.

Examples of the perfluoroalkane include perfluoromethane, perfluoroethane, perfluorobutane, perfluoroisobutane, perfluoroisopropane and the like.

Examples of the compound in which at least one of the fluorine atoms of the perfluoroalkane is substituted with at least one selected from other halogen atoms, hydrogen atoms, and hydroxyl groups include, for example, Freon 12 (= dichlorodifluoromethane), Freon 22 ( = Chlorodifluoromethane), freon 113 (= 1,1,2-trifluorotrichloroethane), C ₆ F ₁₃ H, C ₈ F ₁₇ H, C ₈ F ₁₆ H ₂ , C ₁₀ F ₂₁ H, C ₆ F ₁₃ Br, C ₈ F ₁₇ Br, C ₈ F ₁₆ Br ₂ , C ₆ F ₁₃ CBr ₂ CH ₂ Br, C ₆ F ₁₃ CH = CHC ₆ H ₁₃ (boiling point 195 ° C.), C ₈ F ₁₇ CH = CHC ₈ H ₁₇ mag.

Examples of the perfluorocycloalkane include perfluorodecalin, perfluoromethyldecalin, perfluorodimethyldecalin, perfluoroisopropyldecalin, perfluoro-n-butyldecalin, perfluoromethyladamantane, perfluorodimethyladamantane, perfluoromethylmethyl. Trimethylbicyclo [3.3.1] nonane, perfluorodimethylbicyclo [3.3.1] nonane, perfluorotrimethylbicyclo [3.3.1] nonane, perfluoroperhydrophenanthrene (boiling point 215 ° C.), perfluoro fluorocarbon Perhydrofluoranthene (boiling point 240 ° C.), perfluoroperhydrofluorene (boiling point 194 ° C.), perfluorodiisopropyldecalin, perfluoro-n-butyldecalin, perfluorodisilane Silylmethane, perfluorodixylethane, perfluoroperhydrophenanthrene (trade name "APF-215TM" (boiling point 215 ° C), "APF-240TM" (boiling point 216 ° C), "APF-260TM" (boiling point 260 ° C), or more Air Products (USA)) and the like.

As a compound in which at least one of the fluorine atoms of the perfluoroalkane is substituted by at least one selected from other halogen atoms, hydrogen atoms, and hydroxyl groups, for example, 1-bromo-4-perfluoroisopropylcyclohexane etc. It can be mentioned.

Examples of the perfluoroether include (CF ₃ ) ₂ CFO (CF ₂ ) ₄ F, (CF ₃ ) ₂ CFO (CF ₂ ) ₆ F, [CF ₃ (CF ₂ ) _u ] ₂ O, (u = 3, 5, or 7).

Examples of the perfluoropolyether include (CF ₃ ) ₂ CFO (CF ₂ ) ₄ OCF (CF ₃ ) ₂ , (CF ₃ ) ₂ CFO (CF ₂ ) ₆ OCF (CF ₃ ) ₂ , CF ₃ (OCF) ₂ CF ₂ ) _p (OCF ₂ ) _q CF ₃ (p / q = 0.6 to 0.7), CF ₃ (OC (CF ₃ )) _s F (integer of 2 or more), (CF ₃ ) ₂ CF (OCF ₂ ) _t F (t is an integer of 2 or more) or the like.

As a compound in which at least one of the fluorine atoms of the perfluoropolyether is substituted with at least one selected from other halogen atoms, hydrogen atoms, and hydroxyl groups, for example, CF ₃ O (CF ₂ CF ₂ O) _v Examples include CF ₂ CH ₂ OH (v = 2 or 3), F [CF (CF ₃ ) CF ₂ O] ₂ CHFCF _{3 and the} like.

Examples of the perfluoroamines include N (C ₃ F ₇ ) ₃ , N (C ₄ F ₉ ) ₃ (boiling point 178 ° C.), N (C ₅ F ₁₁ ) ₃ and perfluoro-N-methylperhydroquinoline. And perfluoro-N-methylperhydroisoquinoline and the like.

The molecular weight of the compound (A) is, for example, 50 to 10000, preferably 100 to 8000, particularly preferably 500 to 8000, and most preferably 1000 to 7000.

The compound (A) has a boiling point of, for example, 140 ° C. or more, preferably 200 ° C. or more (eg, 200 to 300 ° C.) at normal pressure, which is less volatile at room temperature and suitable for use in the form of external preparations Preferred.

In applications where rapid evaporation of compound (A) is required, lower boiling point can be used.

Among the compounds (A), at least one selected from perfluoroalkanes, perfluorocycloalkanes, perfluoroethers, perfluoropolyethers, and perfluoroamines, among others, feel in use, water repellency, And the use of perfluoropolyethers is particularly preferred, and perfluoropolyethers having a molecular weight of 500 to 8000 (most preferably 1000 to 7000) are particularly preferred.

(Compound (B))
The compound (B) in the present invention is a compound represented by the following formula (b) and having a perfluoroalkyl chain moiety and a hydrocarbon chain moiety, and is a compound having a surface activity ability (ie, a surfactant). is there. The compound (B) in the present invention is used as a gelling agent for the above compound (A).

(Wherein, m1 and m2 are the same or different and each represents an integer of 3 to 22. Y represents a hydrogen atom or a hydroxyl group)

M1 in the formula (b) represents an integer of 3 to 22. In the present invention, among them, in view of gelling ability and solubility, it is preferably an integer of 5 to 18, particularly preferably an integer of 7 to 15.

M2 in the formula (b) represents an integer of 3 to 22. In the present invention, among them, in view of gelling ability and solubility, it is preferably an integer of 5 to 18, particularly preferably an integer of 6 to 15.

In the formula (b), m1 + m2 is, for example, an integer of 10 to 40, preferably an integer of 12 to 35, and particularly preferably an integer of 15 to 30.

Specific examples of the compound (B) in the case where Y is a hydroxyl group are 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 21, 21, 21 1 -Henicosa fluorohenicosan -1-ol, 11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 20-henicosafluoroicosan-1-ol, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 13, 13, 14, 14 , 15, 15, 16, 16, 17, 17, 17-17-Henichosa fluoroheptadecane-1-ol, 9, 9, 10, 10, 11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 1 , 19, 20, 20, 20-pentacosafluoroicosane-1-ol, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 17-tridecafluoroheptadecane -1-ol, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 13, 13, 13-tridecafluorotridecane-1-ol, 13, 13, 14, 14, 15 , 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 21, 21, 22, 22, 23, 23, 24, 24, 24-pentacosafluorotetracosan-1-ol Etc.

Specific examples of the compound (B) when Y is a hydrogen atom are 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8 9, 9, 10, 10-Henicosa fluorohenicosan, 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8 9, 9, 10, 10-Henicosa fluoroicosane, 1, 1, 1, 2, 2, 3, 3, 4, 5, 4, 5, 6, 7, 7, 8, 8, 9,9,10,10-Henicosa fluoroheptadecane, 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoroheptadecane, 1,1 1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorotridecane, 1,1,1,2,2,3,3,4,4,5,5 , 6, 6, 7, 7, 8, 8, 9, 9, 10, 10, 11, 1 , 12, 12-Pentacosafluorotetracosane, 1, 1, 1, 2, 2, 3, 3, 4, 5, 4, 5, 6, 6, 7, 7, 8, 8, 9, 9, 10 10, 11, 11, 12, 12, 12-pentacosafluoroicosane and the like.

The compound (B) is a compound comprising a perfluoroalkyl chain moiety and a hydrocarbon chain moiety as described above, and the perfluoroalkyl chain moiety has affinity to the compound (A). Therefore, when compound (B) is added to compound (A) and compatibilized, compound (B) is assembled with compound (A) with the perfluoroalkyl chain part on the outside and the hydrocarbon chain part on the inside. It is possible to form a body (for example, a string-like association), and the assembly forms a network in the compound (A), whereby the compound (A) is gelled. In addition, since the inside of the assembly has a hydrophilic environment, it is also possible to enclose, for example, a water-soluble substance.

In addition, Compound (B) has lower hemolytic activity and lower toxicity as compared to hydrocarbons similar to Compound (B) (JG Riess, Adv. Mat., 3: 249-251 (1991)). Therefore, it is excellent in biocompatibility and can be used in the fields of pharmaceuticals, quasi-drugs and cosmetics.

The compound (B) can be produced, for example, by the following method and the like, but is not limited to this production method. Although the perfluoroalkyl iodide represented by the formula (1) is used in the following method, it is also possible to use perfluoroalkyl bromide or perfluoroalkyl chloride instead. In the following formulas, Y, m1 and m2 are the same as above.

The above step [1] is a step of reacting (radical reaction) the perfluoroalkyl iodide represented by the formula (1) with the unsaturated compound represented by the formula (2). The compound represented by the said Formula (3) is obtained through the said process [1].

The above reaction may be carried out without a solvent, but it is preferable to carry out the reaction in the presence of a solvent in terms of facilitating the production operation. The solvent is particularly limited as long as it is excellent in the solubility of the perfluoroalkyl iodide represented by the formula (1) and the unsaturated compound represented by the formula (2) and does not inhibit these radical reactions. For example, aromatic hydrocarbons such as toluene; ethers such as THF; esters such as butyl acetate; ketones such as methyl ethyl ketone; alcohols such as propanol; and the like. These can be used singly or in combination of two or more.

The amount of the solvent used is, for example, about 50 to 300% by weight, preferably about 100% by weight, based on the total amount of the perfluoroalkyl iodide represented by the formula (1) and the unsaturated compound represented by the formula (2). It is ̃300% by weight. When the amount of the solvent used exceeds the above range, the concentration of the reaction component tends to be low, and the reaction rate tends to be low.

Moreover, it is preferable to carry out the above reaction in the presence of a radical initiator in that the progress of the reaction can be promoted. Examples of the radical initiator include, for example, azo compounds [for example, 2,2′-azobis (isobutyronitrile), 2,2′-azobis (2,4-dimethylvaleronitrile, azobiscyanovaleric acid, 2,2′- Azobis (2-amidinopropane) hydrochloride, 2,2′-azobis (2-amidinopropane) acetate, etc.], inorganic peroxides (eg, persulfates such as potassium persulfate, sodium persulfate, ammonium persulfate, etc.) Hydrogen peroxide), organic peroxides [eg, benzoyl peroxide, di-t-butyl peroxide, cumene hydroperoxide, bis (2-ethoxyethyl) peroxydicarbonate], redox catalysts, etc. These can be used alone or in combination of two or more.

The atmosphere for the reaction is not particularly limited as long as the reaction is not inhibited. For example, any of an air atmosphere, a nitrogen atmosphere, an argon atmosphere and the like may be used.

The reaction temperature can be appropriately adjusted depending on the solvent used and is, for example, about 60 to 120 ° C. The reaction time is, for example, about 0.1 to 20 hours. After completion of the reaction, an aging step may be provided. When the ripening step is provided, the ripening temperature is, for example, about 60 to 100 ° C., and the ripening time is, for example, about 0.1 to 5 hours. The reaction can be carried out by any method such as batch system, semi-batch system, continuous system and the like.

After completion of the reaction, the obtained reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, adsorption, recrystallization, column chromatography, or a combination of these.

The step [2] is a step of subjecting the compound represented by the formula (3) obtained through the above step [1] to a reduction treatment to obtain a compound (B).

The reduction treatment of the compound represented by the formula (3) can be carried out by a well-known and commonly used method, for example, a reduction method using a hydrogenation reducing agent.

Examples of the hydrogenation reducing agent include metals such as zinc and tin; aluminum hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, diisobutylaluminum hydride, dibutyltin hydride, tributyltin hydride, hydrogen Diphenyltin halide, triphenyltin hydride, zinc borohydride, diborane and the like can be mentioned.

The reduction treatment may be carried out in the presence of a solvent, and examples of the solvent include alcohols such as methanol, ethanol and isopropanol and their aqueous solutions, diglyme and their aqueous solutions, sulfolane, pyridine, DMSO, THF and the like. it can. These can be used singly or in combination of two or more.

The amount of the solvent used is, for example, about 50 to 300% by weight, preferably 100 to 300% by weight, relative to the compound represented by the formula (3). When the amount of the solvent used exceeds the above range, the concentration of the reaction component tends to be low, and the reaction rate tends to be low.

The reaction temperature can be appropriately adjusted depending on the solvent used and is, for example, about 60 to 100 ° C. The reaction time is, for example, about 0.1 to 20 hours. After completion of the reaction, an aging step may be provided. When the aging step is provided, the aging temperature is, for example, about 10 to 40 ° C., and the aging time is, for example, about 0.5 to 5 hours. The reaction can be carried out by any method such as batch system, semi-batch system, continuous system and the like.

(Method of producing gel composition)
The gel composition of the present invention comprises the step of compatibilizing at least one of the compound (A) represented by the formula (a) and at least one of the compound (B) represented by the formula (b) It can be manufactured simply.

The compound (A) and the compound (B) are compatibilized by, for example, heat mixing at 80 to 200 ° C. (preferably 100 to 180 ° C., particularly preferably 120 to 160 ° C.) to form a compatibilized substance . In addition, the compound (A) and the compound (B) may be prepared by mixing the compound (A) and the compound (B) in advance and then heating the compound (A) to make the compound compatible. The compound (B) may be gradually added thereto to be compatible. Furthermore, it is preferable to perform stirring processing at the time of heating. If necessary, a degassing treatment (for example, degassing treatment by centrifugation at room temperature) may be performed.

The time required for heating is, for example, about 3 to 60 minutes (preferably 10 to 30 minutes).

After heating, it is preferable to cool to room temperature (eg, 1 to 30 ° C.) or less. The cooling may be gradual cooling at room temperature or may be rapid cooling by ice cooling or the like.

The amount of compound (B) used is, for example, 0.1 to 33 parts by weight, preferably 0.5 to 25 parts by weight, particularly preferably 1 to 18 parts by weight, per 100 parts by weight of compound (A). Preferably, it is 2 to 11 parts by weight. The weight ratio of the amount of compound (A) to compound (B) used (the former: the latter) is, for example, 75:25 to 99.9: 0.1, preferably 80:20 to 99.5: 0. .5, particularly preferably 85:15 to 99: 1, most preferably 90:10 to 98: 2. The compound (B) has excellent surfactant activity with respect to the compound (A), so that the compound (A) can be gelled by using a very small amount. If the amount of the compound (B) used falls below the above range, it may be difficult to stably maintain the viscosity, such as viscosity reduction due to temperature change. On the other hand, even if the amount of compound (B) used exceeds the above range, no further improvement in the effect is observed, which is uneconomical.

The proportion of the component derived from the compound (A) in the total amount of constituents of the obtained compatible material is 75 to 99.9% by weight, preferably 80 to 99.5% by weight, particularly preferably 85 to 99% by weight. Most preferably, it is 90 to 98% by weight.

Accordingly, the proportion of the component derived from compound (B) in the total amount of the components of the compatible material is 0.1 to 25% by weight, preferably 0.5 to 20% by weight, particularly preferably 1 to 15% by weight. %, Most preferably 2 to 10% by weight.

In addition, the proportion of the component derived from the compound (A) in the gel composition of the present invention is, for example, 30 to 99.9% by weight, preferably 50 to 99.9%, more preferably 75 to 99.9%. More preferably, it is 80 to 99.5% by weight, particularly preferably 85 to 99% by weight, and most preferably 90 to 98% by weight.

The proportion of the component derived from compound (B) in the total amount of gel composition of the present invention is, for example, 0.1 to 70% by weight, preferably 0.1 to 50% by weight, more preferably 0.1 to 25%. % By weight, more preferably 0.5 to 20% by weight, particularly preferably 1 to 15% by weight, most preferably 2 to 10% by weight.

In addition, the gel composition of the present invention may contain other components as needed as long as the effects of the present invention are not impaired, besides the compatibilizer of the compound (A) and the compound (B). The proportion of the compatibilizer of the compound (A) and the compound (B) in the whole gel composition of the present invention is, for example, 5% by weight or more, preferably 10% by weight or more. It is preferably at least 20% by weight, more preferably at least 30% by weight, still more preferably at least 40% by weight, still more preferably at least 50% by weight, still more preferably at least 60% by weight, particularly preferably at least 70% by weight, particularly preferably It is at least 80% by weight, most preferably at least 90% by weight. The upper limit is 100% by weight. That is, the gel composition of the present invention may consist of only the compatibilizer of the compound (A) and the compound (B).

Moreover, as another component which the gel-like composition of this invention may contain, any of an oil-based component and an aqueous component may be sufficient, and it can adjust suitably according to a use. For example, when the gel composition of the present invention is used as a drug, quasi drug or cosmetic product, it can contain, without particular limitation, components usually contained in the drug, quasi drug or cosmetic product. In particular, when the gel composition of the present invention is used as a drug, quasi-drug or cosmetic product, it contains a substance (eg, growth factor, antibiotic, nutrient, etc.) to be released at an appropriate site. It may be done.

In addition, the gel composition of the present invention may contain other oily components in addition to the compound (A), but the content of the oily components other than the compound (A) (when two or more kinds are contained, The total amount is, for example, 60% by weight or less, preferably 50% by weight or less, more preferably 40% by weight or less, still more preferably 30% by weight or less, particularly preferably 20% by weight or less of the total amount of oil components contained in the gel composition Particularly preferably, it is at most 10% by weight, most preferably at most 5% by weight. The lower limit is 0% by weight.

Furthermore, the gel composition of the present invention may contain a surfactant other than the compound (B), but the content of the surfactant other than the compound (B) (in the case of containing two or more, the total amount thereof ) Is, for example, 40% by weight or less, preferably 30% by weight or less, more preferably 20% by weight or less, particularly preferably 10% by weight or less, most preferably 5% by weight or less of the total amount of surfactant contained in the gel composition It is. The lower limit is 0% by weight. In the present specification, a surfactant is a compound having a high affinity functional group to an oil component and a low affinity functional group in combination.

The gel composition of the present invention has high viscosity and no flowability. The viscosity at 25 ° C. [at a shear rate of 0.5 s ⁻¹ ] is, for example, 10 Pa · s or more, preferably 20 Pa · s or more.

The gel composition of the present invention contains the compound (B) having an excellent surface activity ability, and therefore, when the compound (A) is transparent, it exists as a transparent gel composition. Therefore, the gel composition of the present invention is excellent in appearance.

The gel composition of the present invention is excellent in stability and extremely inactive chemically and biologically. Further, they are stable to heat, and the compatibilizer contained in the gel-like composition of the present invention even after heat sterilization etc., that is, an aggregate of compound (A) and compound (B) (for example, a string (Like aggregate) can maintain high viscosity without reducing molecular weight. Therefore, it can be used also in the field where high hygiene management is required.

The gel composition of the present invention contains a high concentration of the compound (A) excellent in the solubility of gas (for example, oxygen, carbon dioxide, air), and therefore means for delivering a high concentration of gas to the application site It can be suitably used as

In addition, the gel-like composition of the present invention contains a compound (A) which is both hydrophobic and oleophobic and is excellent in gas permeability at a high concentration. Therefore, by applying and drying the gel-like composition of the present invention, it is possible to form a protective film having both hydrophobicity and oleophobicity while having gas (especially oxygen) permeability. Accordingly, the gel composition of the present invention can also be suitably used as a film forming agent.

Furthermore, the gel-like composition of the present invention has lubricating properties, has an effect of improving sliding and suppressing friction.

Therefore, the gel composition of the present invention can be suitably used as a medicine, quasi-drug, cosmetics, or lubricant. When the gel composition of the present invention is used as a medicine, quasi-drug, cosmetics, or lubricant, it has high viscosity and does not have fluidity, so it is excellent in usability or applicability.

When the gel composition of the present invention is a pharmaceutical product, quasi-drug or cosmetic product, it may be used by applying directly to the skin, patch applied to the skin, transdermal patch, plaster, bandage It may be used by impregnating with a support such as an agent.

In particular, when the gel composition of the present invention is a pharmaceutical product or quasi-drug product, if it is applied to the affected area, the affected area is protected from contamination and dust while maintaining the permeability of gas (especially oxygen). Can form a coating. In addition, when the gel composition of the present invention is a cosmetic, if it is applied to the skin, while maintaining the permeability of gas (especially oxygen) (that is, without inhibiting skin respiration), the skin surface And the like can be concealed to form a film capable of evenly conditioning the skin surface.

EXAMPLES The present invention will be described in more detail based on examples given below, but the invention is not meant to be limited by these examples.

Preparation Example 1 [gelling Agent (1): 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 21, 21] Synthesis of 1,21-Henicosa fluorohenicosan-1-ol]
[Step 1]
In a 100 mL eggplant flask, 9.680 g (15 mmol) of perfluorodecyl iodide, 5.123 g (30.1 mmol) of 10-undecen-1-ol, and 5 mL of dehydrated toluene are added, and 90 is introduced through an inlet tube under argon gas flow. Stir at ° C.
About 20 mg of 2,2'-azobis (isobutyronitrile) in the reaction mixture about 8 times every about 30 to 45 minutes, using ¹ H-NMR and GC / MS to complete the reaction of perfluorodecyl iodide Was added until confirmed.
After completion of the reaction, toluene (30 mL) was added to the reaction mixture and stirred at 80 ° C. for 30 minutes. The mixture is allowed to stand at room temperature and allowed to cool to room temperature over the course of a day, and the precipitated white solid is filtered and separated, toluene (30 mL) is added again, and 10-undecen-1-ol is obtained by ¹ H-NMR. The above operation was repeated until the peak derived from double bond disappeared (total 3 times).
The obtained white residue is dried, and 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 21, 21, 21 There were obtained 7.631 g (9.35 mmol, yield 62%) of 21-henicosfluoro-10-iodohenicosan-1-ol.

[Step 2]
The above 12,12,13,13,14,14,15,15,16,16,17,17,18,19,19,20,20,21,21,21-Heniko Add 7.030 g (8.6 mmol) of safluoro-10-iodohenicosan-1-ol and ethanol, and introduce it through a flask in which argon gas is bubbled in concentrated hydrochloric acid using an inlet tube, and exhaust The side was passed through an alkali trap and vigorously stirred in an 80 ° C. oil bath.
0.3 g of powdered zinc was added to the reaction mixture in six portions. The mixture was heated at 40 ° C. in an oil bath and bubbling of argon gas was stopped. Isopropyl ether (100 mL) and deionized water (100 mL) were added to the reaction mixture and vigorously stirred for 30 minutes, and then allowed to stand at room temperature. The organic layer was transferred to a separatory funnel, washed with saturated aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (30 mL) (twice each), and the organic layer was dried with a desiccant (anhydrous magnesium sulfate) for 15 minutes.
The drying agent was filtered off, concentrated by an evaporator, dissolved by heating in toluene (100 mL) and allowed to cool at room temperature while stirring. The precipitated white precipitate is separated by suction filtration, dried by an evaporator, and represented by the following formula (b-1), as a white solid gelling agent (1) (12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 21, 21, 21-Henicosa fluorohenicosan-1-ol) 4.83 g (7. 0 mmol, yield 82%) was obtained. The structure of the reaction product was confirmed by ¹ H-NMR.
¹ H-NMR (400 MHz, CDCl ₃ ): δ = 3.65 (t, 2 H), 2.05 (m, 2 H), 1.56 (m, 4 H), 1.29 (m, 14 H), 1.20 (t, 1 H)

Preparation Example 2 [gelling Agent (2): 11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20] , 20-Synthesis of fluoro icosane-1-ol]
A compound represented by the following formula (b-2) in the same manner as in Preparation Example 1 except that 9-decene-1-ol was used instead of 10-undecen-1-ol in Step 1 of Preparation Example 1. Gelling agent (2) (11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 20-hen Eicosafurolicocosan-1-ol) 2.284 g, 3.38 mmol, 94% yield was obtained.
¹ H-NMR (400 MHz, CDCl ₃ ): δ = 3.64 (t, 2 H), 2.05 (m, 2 H), 1.57 (m, 4 H), 1.30 (m, 12 H), 1.20 (t, 1 H)

Preparation Example 3 [gelling Agent (3): 9, 9, 10, 10, 11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18] , 19, 19, 20, 20, 20-Synthesis of pentacosafluoroicosane-1-ol]
The same procedure as in Preparation Example 1 is repeated, except that perfluorododecyl iodide is used in place of perfluorodecyl iodide and 7-octene-1-ol is used in place of 10-undecen-1-ol in Preparation Example 1. And a gelling agent (3) (9, 9, 10, 10, 11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16) represented by the following formula (b-3) , 16, 17, 17, 18, 18, 19, 19, 20, 20, 20-pentacosafluoroicosan-1-ol) (1.23 g, 1.65 mmol, yield 47%).
¹ H-NMR (400 MHz, CDCl ₃ ): δ = 3.65 (t, 2 H), 2.03 (m, 2 H), 1.58 (m, 4 H), 1.30 (m, 8 H), 1.20 (t, 1 H)

Preparation Example 4 [gelling agent (4): 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10 Synthesis of 10,11,11,11,12,12-Pentacosafluorotetracosane]
In the same manner as in Preparation Example 1 except that perfluorododecyl iodide was used instead of perfluorodecyl iodide and 1-dodecene instead of 10-undecen-1-ol was used in place of perfluorodecyl iodide in Preparation Example 1; The gelling agent (4) (1, 1, 1, 2, 2, 3, 3, 4, 5, 4, 5, 6, 7, 7, 8, 8) represented by (b-4) , 9, 9, 10, 10, 11, 11, 12, 12-pentacosafluorotetracosane) 1.23 g, 1.65 mmol, yield 47%) was obtained.
¹ H-NMR (400 MHz, CDCl ₃ ): δ = 2.05 (m, 2 H), 1.60 (m, 2 H), 1.25-1.42 (m, 18 H), 0.88 (t, 3 H)

Preparation Example 5 [gelling agent (5): 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10 , 10, 11, 11, 12, 12-Synthesis of pentacosafluoroicosane]
In the same manner as in Preparation Example 1 except that perfluorododecyl iodide was used instead of perfluorodecyl iodide and 1-octene instead of 10-undecen-1-ol was used in place of perfluorodecyl iodide in Preparation Example 1; A gelling agent (5) represented by (b-5) (1, 1, 1, 2, 2, 3, 3, 4, 5, 4, 5, 6, 7, 7, 8, 8) , 9, 9, 10, 10, 11, 11, 12, 12-pentacosafluoroicosane) 2.42 g, 3.38 mmol, yield 93%).
¹ H-NMR (400 MHz, CDCl ₃ ): δ = 2.05 (m, 2 H), 1.60 (m, 2 H), 1.25-1.42 (m, 10 H), 0.88 (t, 3 H)

Example 1
1 cm ^{3 of} polyperfluoromethyl isopropyl ether (molecular weight 1500) is added to a test tube, to which 5% by weight of the gelling agent (1) is added and mixed, and heated and stirred at 150 ° C. It was dissolved and cooled to 25 ° C. to obtain a composition (content of polyperfluoromethyl isopropyl ether (molecular weight 1500): 95% by weight).

Examples 2 to 10, Comparative Examples 1 to 6
A composition was obtained in the same manner as in Example 1 except that the formulation was changed as described in the following Table 1 (unit: wt%).

<Evaluation of gelation ability>
The appearances of the compositions obtained in Examples and Comparative Examples were visually observed, and those having fluidity of various flowable organic substances were evaluated as “x”, and those having no fluidity were evaluated as “o”. The results are summarized in Table 1 below.

Each component in Table 1 will be described below.
Polyperfluoromethyl isopropyl ether (molecular weight 1500): manufactured by Solvay, trade name "fonbrin HC / 04", boiling point: 200 to 270 ° C
Polyperfluoromethyl isopropyl ether (molecular weight 6250): manufactured by Solvay, trade name "fonbrin HC / R", boiling point: 200 to 270 ° C
Gelling agents (1) to (5): The products obtained in Preparation Examples 1 to 5 are used Gelling agent (6): 12-hydroxystearic acid, manufactured by Ito Oil Co., Ltd. Gelling agent (7): Di Benzylidene sorbitol, manufactured by Shin Nippon Rika Co., Ltd., trade name "Gelall D"
Gelling agent (8): inulin stearic acid ester, manufactured by Chiba Flour Mills Co., Ltd., trade name "Leopard ISL2"

As a summary of the above, the configuration of the present invention and variations thereof will be additionally described below.
[1] A gel-like composition containing the following compatible substance:
Compatibilizer: compatibilizer of the compound (A) represented by the formula (a) and the compound (B) represented by the formula (b) [or the compound (A) represented by the formula (a) And a mixture obtained by heating and mixing the compound (B) represented by the formula (b) at 80 to 200 ° C.], which is 75 to 99.9% by weight of the total amount of the components of the compatible substance (preferably 80 to 99.5% by weight, particularly preferably 85 to 99% by weight, most preferably 90 to 98% by weight) is a component derived from compound (A) [2] compatible substance [R ^{1 in} formula (a) Is a monovalent saturated aliphatic hydrocarbon group, a monovalent saturated alicyclic hydrocarbon group, and a monovalent group in which two or more of these are bonded via an ether bond, and a carbon atom constituting R ¹ 30% or more of the hydrogen atoms bonded to are groups substituted with a halogen atom containing at least one fluorine atom [1 The gel composition according to.
[3] The compound (A) is a perfluoroalkane, a perfluorocycloalkane, a perfluoroether, a perfluoropolyether, a perfluoroamine, and a halogen atom in which at least one of the fluorine atoms of these compounds is other than a fluorine atom, The gel-like compound according to [1], which is a compound substituted with at least one selected from a hydrogen atom and a hydroxyl group, and having at least one fluorine atom. Composition.
[4] The gel composition according to [1], wherein the compound (A) is at least one selected from perfluoroalkanes, perfluorocycloalkanes, perfluoroethers, perfluoropolyethers, and perfluoroamines. object.
[5] The gel composition according to [1], wherein the compound (A) is a perfluoropolyether.
[6] The gel composition according to any one of [1] to [5], wherein the molecular weight of the compound (A) is 1000 to 10000 (preferably 1000 to 8000, particularly preferably 1000 to 7000).
[7] The gel composition according to any one of [1] to [6], which has a boiling point of 140 to 300 ° C. (preferably 200 to 300 ° C.) under normal pressure of the compound (A).
[8] a compound wherein the compound (B) is represented by the formula (b), m1 in the formula (b) is an integer of 7 to 15, m2 is an integer of 5 to 15, and m1 + m2 is an integer of 15 to 30 The gel composition according to any one of [1] to [7].
[9] The compound (B) is at least one selected from the compounds represented by formulas (b-1), (b-2), (b-3), (b-4) and (b-5) The gel composition according to any one of [1] to [7], which is one type.
[10] 0.1 to 25% by weight (preferably 0.5 to 20% by weight, particularly preferably 1 to 15% by weight, most preferably 2 to 10% by weight) of the total amount of the components of the compatibilizing agent is the compound (B The gel composition according to any one of [1] to [9], which is a component derived from the above.
[11] The proportion of the compatibilizer of compound (A) and compound (B) in the total amount of gel-like composition is 5 to 100% by weight (the lower limit is preferably 10% by weight, more preferably 20% by weight, further preferably) Is 30% by weight, more preferably 40% by weight, more preferably 50% by weight, more preferably 60% by weight, particularly preferably 70% by weight, particularly preferably 80% by weight, most preferably 90% by weight) The gel composition according to any one of [1] to [10].
[12] The proportion of the compound (A) in the total amount of oily components contained in the gel-like composition is 40% by weight or more (preferably 50% by weight or more, more preferably 60% by weight or more, still more preferably 70% by weight or more) The gel composition according to any one of [1] to [11], which is particularly preferably at least 80% by weight, particularly preferably at least 90% by weight, most preferably at least 95% by weight.
[13] The proportion of the compound (B) in the total amount of compounds having a high affinity functional group to an oily component and a high affinity functional group to an aqueous component contained in the gel-like composition is 40% by weight or more (Preferably 50 wt% or more, more preferably 60 wt% or more, still more preferably 70 wt% or more, particularly preferably 80 wt% or more, particularly preferably 90 wt% or more, most preferably 95 wt% or more) The gel composition according to any one of [1] to [12].
[14] The gel composition according to any one of [1] to [13], which has a viscosity of 10 Pa · s or more (preferably 20 Pa · s or more) at 25 ° C. and a shear rate of 0.5 s ⁻¹ . .
[15] The gel composition according to any one of [1] to [14], which is a medicine, quasi-drug, cosmetics, or a lubricant.
[16] Use of the gel composition according to any one of [1] to [14] as a medicine, quasi-drug, cosmetics, or lubricant.
[17] The gel composition according to any one of [1] to [15], which is a film forming agent [18] The gel composition according to any one of [1] to [15] Use as a film forming agent.

The gel composition of the present invention has high viscosity and no flowability. In addition, they are excellent in stability and extremely inactive chemically and biologically. Furthermore, the solubility and permeability of the gas are excellent. Furthermore, the gel composition of the present invention is stable to heat, and can maintain its viscosity high even after heat sterilization and the like. Therefore, it can be suitably used as pharmaceuticals, quasi-drugs, cosmetics, lubricants and the like.

Claims

The gel-like composition containing the following compatibles.
Compatibilizer: the following formula (a)

(Wherein, R 1 represents a monovalent hydrocarbon group or a monovalent group in which two or more hydrocarbon groups are linked via a linking group, and a hydrogen atom of a hydrogen atom bonded to a carbon atom constituting R 1 30% or more is substituted by a halogen atom containing at least one fluorine atom, X is a halogen atom, a hydrogen atom, a nitrogen atom, or a hydroxyl group, and n is an integer of 1 to 3)
And a compound (A) represented by the following formula (b)

(Wherein, m1 and m2 are the same or different and each represents an integer of 3 to 22. Y represents a hydrogen atom or a hydroxyl group)
Compatibilized with the compound (B), wherein 75 to 99.9% by weight of the total of the compatibilizer components is a component derived from the compound (A)
The compound (A) is a perfluoroalkane, a perfluorocycloalkane, a perfluoroether, a perfluoropolyether, a perfluoroamine, and at least one of the fluorine atoms of these compounds is a halogen atom other than a fluorine atom, a hydrogen atom, The gel composition according to claim 1, wherein the gel composition is a compound substituted with at least one selected from the group consisting of: and a hydroxyl group, and a compound having at least one fluorine atom.
The gel composition according to claim 1 or 2, which is a medicine, quasi-drug, cosmetics, or a lubricant.
The gel composition according to any one of claims 1 to 3, which is a film forming agent.