Novel hydroxyalkyl methylcellulose and use thereof

Abstract

To provide a hydroxyalkyl methyl cellulose exhibiting improved gel strength at a high temperature.SOLUTION: In the substitution pattern of the hydroxyalkyl groups of the anhydroglucose units of the hydroxyalkyl methyl cellulose, a pattern such that the mole fraction of anhydroglucose units of the hydroxyalkyl methyl cellulose wherein only the hydroxy groups at the 6-positions are substituted with hydroxyalkyl is from 0.01 to 0.1, and in the substitution pattern of the methoxyl groups of the anhydroglucose units of the hydroxyalkyl methyl cellulose, a pattern such that the mole fraction ratio of anhydroglucose units wherein only the hydroxy groups at the 2 - and 3-positions of the anhydroglucose units are substituted with methyl groups / the mole fraction ratio of anhydroglucose units wherein only the hydroxy groups at the 2 - and 6-positions of the anhydroglucose units are substituted with methyl groups is from 0.36 to 0.60.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to novel hydroxyalkyl methylcelluloses and their use for ceramic extrusion, in food compositions and as excipients in oral dosage forms. [Background technology]

[0002] Hydroxyalkyl methylcelluloses, such as hydroxypropyl methylcellulose, are widely used and accepted in pharmaceutical applications, for example, for the production of hard capsules and tablet coatings, or as matrix polymers in tablets, bakery fillings, fried foods, meat and meat analogs, and as organic binders for inorganic materials, particularly ceramic-forming materials.

[0003] Hydroxyalkyl methylcelluloses, such as hydroxypropyl methylcellulose, are known to exhibit reverse thermal gelation in water. In other words, aqueous hydroxypropyl methylcellulose-based materials are soluble at low temperatures and gel at high temperatures. Reverse thermal gelation in water is described in the article "Thermal Gelation" by N. Sarkar, Journal of Applied Polymer Science, Vol. 24, pp. 1073-1087 (1979). This is explained in detail in "Properties of Methyl and Hydroxypropyl Methylcellulose." Specifically, when an aqueous solution of hydroxypropyl methylcellulose is heated, the hydrophobic methoxyl groups localized within the molecule dehydrate, resulting in a hydrogel. On the other hand, when the resulting gel is cooled, the hydrophobic methoxyl groups rehydrate, and the gel returns to its original aqueous solution. Hydroxyalkyl methylcellulose is known to have a lower storage modulus than methylcellulose. Hydroxyalkyl methylcelluloses with a low storage modulus do not form strong gels. Even to form weak gels, high concentrations are required (Haque, A; Richardson, RK; Morris, ER, Gidley, MJ and Caswell, DC, Carbohydrate Polymers 22 (1993) p. 175; and Haque, A and Morris, ER, Carbohydrate Polymers 22 (1993) p. 161. For example, at the same concentration of 2 wt. %, the maximum storage modulus of METHOCEL™ K4M HPMC is typically less than about 100 Pa at elevated temperatures, whereas the maximum storage modulus of METHOCEL™ A4M methylcellulose is typically greater than about 1000 Pa. Summary of the Invention [Means for solving the problem]

[0004] Surprisingly, it has now been found that hydroxyalkyl methyl celluloses can be prepared which, unlike the hydroxyalkyl methyl celluloses disclosed in the above-mentioned documents, exhibit improved gel strength at elevated temperatures.

[0005] Therefore, the present invention provides a hydroxyalkyl methylcellulose, wherein the substitution pattern of hydroxyalkyl groups in anhydroglucose units of the hydroxyalkyl methylcellulose is such that s6 (hydroxyalkyl) is 0.01 to 0.1, where s6 is the molar fraction of anhydroglucose units in the hydroxyalkyl methylcellulose in which the hydroxy group at the 6-position of the anhydroglucose unit is substituted with a hydroxyalkyl, and the substitution pattern of methoxyl groups in the anhydroglucose units of the hydroxyalkyl methylcellulose is such that the s23 / s26 (methyl) ratio is 0.36 to 0.60. s23 is the molar fraction of anhydroglucose units in which only the hydroxy groups at the 2- and 3-positions of the anhydroglucose unit are substituted with methyl, and s26 is the molar fraction of anhydroglucose units in which only the hydroxy groups at the 2- and 6-positions of the anhydroglucose unit are substituted with methyl.

[0006] In a further aspect, the present invention relates to a composition for making an extruded ceramic body, comprising an inorganic material that solidifies as a result of firing or sintering, a hydroxyalkyl methyl cellulose as described herein, and water.

[0007] In yet another aspect, the present invention relates to solid food compositions designed to be heat-processed, comprising the hydroxyalkyl methylcellulose described herein. DETAILED DESCRIPTION OF THE INVENTION

[0008] In the hydroxyalkyl methylcellulose of the present invention, the ether substituents are methyl groups, hydroxyalkyl groups, and optional alkyl groups different from methyl. The hydroxyalkyl groups can be the same or different from each other. Preferably, the hydroxyalkyl methylcellulose contains one or two hydroxyalkyl groups, more preferably one or more hydroxy-C 1~3-alkyl groups such as hydroxypropyl and / or hydroxyethyl. Useful optional alkyl groups are, for example, ethyl or propyl, with ethyl being preferred. Preferred hydroxyalkyl methylcelluloses are hydroxy-C such as hydroxypropyl methylcellulose or hydroxyethyl methylcellulose. 1~3 - alkyl methyl cellulose.

[0009] An essential feature of the novel hydroxyalkyl methylcelluloses believed to be important for their ability to form gels at elevated temperatures is a unique distribution of hydroxyalkyl groups on the anhydroglucose units such that s6(hydroxyalkyl) is 0.01 to 0.1, where s6 is the mole fraction of anhydroglucose units in the hydroxyalkyl methylcellulose in which the hydroxy group at the 6-position of the anhydroglucose unit is replaced by a hydroxyalkyl. In preferred embodiments, the s6(hydroxyalkyl) of the hydroxyalkyl methylcelluloses of the present invention is 0.04 to 0.06. In some embodiments, the s6(hydroxyalkyl) is greater than 0.015, e.g., greater than 0.020, e.g., greater than 0.025, e.g., greater than 0.030, e.g., greater than 0.035, e.g., greater than 0.040. In some embodiments, the s6 (hydroxyalkyl) is less than 0.095, such as less than 0.090, for example less than 0.085, such as less than 0.080, for example less than 0.075, such as less than 0.070, for example less than 0.065, such as less than 0.060.

[0010] Another essential feature of the novel hydroxyalkyl methylcelluloses, which is also believed to be important for their ability to form gels at elevated temperatures, is a unique distribution of methyl groups on the anhydroglucose units, such that s23 / s26 is between 0.36 and 0.60, preferably between 0.40 and 0.48. In some embodiments, the s23 / s26 (methyl) ratio is greater than 0.37, e.g., greater than 0.38, e.g., greater than 0.39, e.g., greater than 0.40. In some embodiments, the s23 / s26 (methyl) ratio is less than 0.59, e.g., less than 0.58, e.g., less than 0.57, e.g., less than 0.56, e.g., less than 0.55, e.g., less than 0.54, e.g., less than 0.53, e.g., less than 0.52, e.g., less than 0.51, e.g., less than 0.50, e.g., less than 0.49, e.g., less than 0.48, e.g., less than 0.47, e.g., less than 0.46.

[0011] In the ratio s23 / s26, s23 is an anhydroglucose unit in which only the two hydroxy groups at the 2- and 3-positions of the anhydroglucose unit are substituted with methyl groups. s23 is the mole fraction of anhydroglucose units in which only two hydroxy groups at the 2- and 6-positions of the anhydroglucose unit are substituted with methyl groups, and s26 is the mole fraction of anhydroglucose units in which only two hydroxy groups at the 2- and 3-positions of the anhydroglucose unit are substituted with methyl groups. With regard to the determination of s23, the term "molar fraction of anhydroglucose units in which only two hydroxy groups at the 2- and 3-positions of the anhydroglucose unit are substituted with methyl groups" means that the 6-position is not substituted with methyl; for example, they may be unsubstituted hydroxy groups, or they may be substituted with a hydroxyalkyl group, a methylated hydroxyalkyl group, an alkyl group other than methyl, or an alkylated hydroxyalkyl group. With regard to the determination of s26, the term "molar fraction of anhydroglucose units in which only two hydroxy groups at the 2- and 6-positions of the anhydroglucose unit are substituted with methyl groups" means that the 3-position is not substituted with methyl; for example, they may be unsubstituted hydroxy groups, or they may be substituted with a hydroxyalkyl group, a methylated hydroxyalkyl group, an alkyl group other than methyl, or an alkylated hydroxyalkyl group.

[0012] Formulas I and II below show the numbering of the hydroxy groups in the anhydroglucose unit: Formulas I and II are used for illustrative purposes only and do not represent the hydroxyalkyl methylcellulose of the present invention. [ka] [ka]

[0013] The hydroxyalkyl methylcellulose preferably has a DS(methyl) of 1.0 to 2.0, more preferably 1.2 to 1.8. The degree of methyl substitution of a cellulose ether, DS(methyl), is the average number of OH groups substituted by methyl groups per anhydroglucose unit.

[0014] Hydroxyalkyl methylcellulose has a viscosity of 0.05 to 0.5, preferably 0.1 to 0. It has an MS (hydroxyalkyl) of 3. The degree of hydroxyalkyl substitution is described by the MS (molar substitution), which is the average number of hydroxyalkyl groups attached by ether bonds per mole of anhydroglucose unit. During hydroxyalkylation, multiple substitutions can result in side chains.

[0015] Determination of % methoxyl and % hydroxypropoxy in hydroxypropyl methylcellulose is performed according to the United States Pharmacopoeia (USP 32).

[0016] The values ​​obtained are % methoxyl and % hydroxypropoxy. These are then converted to the degree of substitution (DS) for the methyl substituent and the molar substitution (MS) for the hydroxypropyl substituent. Residual amounts of salts were taken into account in the conversion. The DS (methyl) and MS (hydroxyethyl) of hydroxyethyl methylcellulose were determined by Zeise cleavage with hydrogen iodide followed by gas chromatography. (G. Bartelmus and R. Ketterer, Z. Anal. Chem. 286; 1977: 161-190)

[0017] In one embodiment of the present invention, the viscosity of the hydroxyalkyl methylcellulose is measured using an Anton Paar Physica MCR501 rheometer with a cup and bob geometry (CC-27) at 20°C and a shear rate of 2.51 s -1 and a viscosity of 150 mPa·s to 100,000 mPa·s, as determined by measuring a 2 wt % aqueous solution at 20° C. Hydroxyalkyl methylcelluloses with such viscosities are useful in a variety of applications, such as as food ingredients, for ceramic extrusion, and as excipients in oral dosage forms.

[0018] Surprisingly, it has been found that preferred embodiments of the hydroxyalkyl methylcellulose of the present invention, having a viscosity of greater than 150 mPa·s measured as a 2 wt% aqueous solution at 20°C as defined above, do not precipitate at high temperatures as a 2 wt% solution, unlike conventional hydroxyalkyl methylcellulose grades. In contrast, the hydroxyalkyl methylcellulose of the present invention has been found to exhibit gelation temperatures in the range of 55 to 85°C. The gelation temperature is the temperature at which G' / G" = 1, where G' is the storage modulus and G" is the loss modulus of a 2 wt% aqueous solution of the cellulose ether. Figure 1 shows the gelation temperatures of the hydroxyalkyl methylcelluloses of the present invention. To characterize the temperature dependence of gelation of 2 wt% aqueous solutions of the cellulose ethers, an Anton Paar Physica MCR501 rheometer (Ostfildern, Germany) equipped with a cup-and-bob configuration (CC-27) and a Peltier temperature control system was used under oscillatory shear flow. Measurement details are described in the Examples section. Surprisingly, it has been found that gelation occurs within a narrow temperature interval, such as within a 10°C interval, and is manifested as an abrupt increase in storage modulus G' of at least 5-fold, and even at least 10-fold, at the crossover of G' = G" within the 10°C temperature interval. Such abrupt increase in storage modulus G' is advantageous in applications where a wide temperature window before gelation occurs facilitates stable processing, for example, when the hydroxyalkyl methylcellulose is used as an ingredient in ceramic extrusions or in solid food products designed for heat processing.

[0019] Also, surprisingly, as defined above, at 20°C and a shear rate of 2.51 s -1 It has also been surprisingly found that the hydroxyalkyl methyl cellulose of the present invention, having a viscosity of more than 150 mPa·s determined as a 2 wt. % aqueous solution at 20°C and a shear rate of 2.51 s, has a high gel strength. Gel strength is measured as the storage modulus G' when an aqueous solution of the hydroxyalkyl methyl cellulose is characterized by G' / G" ≥ 1, i.e., when it forms a gel. -1The hydroxyalkyl methylcellulose of the present invention having a viscosity of more than 150 mPa·s, determined as a 2% by weight aqueous solution, is usually in the range of 10 to 10,000 Pa, for example, in the range of 12 to 9,500 Pa, for example, in the range of 14 to 9 000 Pa, for example, in the range of 16 to 8500 Pa, for example, in the range of 18 to 8000 Pa, for example, in the range of 20 to 7500 Pa, for example, in the range of 23 to 7000 Pa, for example, in the range of 25 to 7000 Pa, for example, in the range of 10 to 5000 Pa, for example, in the range of 25 to 5000 Pa, for example, in the range of 30 to 5000 Pa, for example, in the range of 40 to 5000 Pa, for example, in the range of 50 to 5000 Pa, for example, in the range of 60 to 5000 Pa, for example, in the range of 70 to 5000 Pa, for example, in the range of 80 to 5000 Pa, for example, in the range of 90 to 5000 Pa.

[0020] The storage modulus G', loss modulus G'', and gelation temperature at G' / G'' = 1 of 2 wt% aqueous solutions of cellulose ethers were measured in a temperature sweep experiment using an Anton Paar Physica MCR 501 with a Peltier temperature control system under oscillatory shear flow. A cup-and-bob geometry (CC-27) was used. Measurements were performed at a constant frequency of 2 Hz from 20 to 85 °C with a constant strain (deformation amplitude) of 0.5%. These measurements were performed at a heating rate of 1 °C / min and a data collection rate of 4 points / min. The storage modulus G' obtained from the oscillatory measurements represents the elastic properties of the solution. The loss modulus G'' obtained from the oscillatory measurements represents the viscous properties of the solution. During the gelation process of the sample, G' exceeds G''. The intersection of G' and G'' represents the gelation temperature.

[0021] The novel methods for producing the hydroxyalkyl methylcelluloses of the present invention are described in detail in the Examples. Some aspects of the novel methods for producing the hydroxyalkyl methylcelluloses are described in more general terms below.

[0022] Generally, the cellulose pulp, or partially reacted cellulose pulp as the reaction of the cellulose pulp to hydroxyalkyl methylcellulose proceeds, is alkalized in two or more stages, preferably two or three stages, in one or more reactors containing an aqueous alkaline solution of an alkali metal hydroxide, more preferably sodium hydroxide. The aqueous alkaline solution preferably has an alkali metal hydroxide content of 30 to 70 percent, more preferably 35 to 60 percent, and most preferably 48 to 52 percent, based on the total weight of the aqueous alkaline solution.

[0023] In one embodiment, an organic solvent such as dimethyl ether is added to the reactor as a diluent and coolant. Similarly, the reactor headspace is optionally purged with an inert gas (such as nitrogen) to control oxygen-catalyzed depolymerization of the cellulose ether product.

[0024] Typically, 1.2 to 5.0 molar equivalents of alkali metal hydroxide are added per mole of anhydroglucose unit in the cellulose in the first stage. Uniform swelling and distribution of the pulp are optionally controlled by mixing and stirring. The rate of addition of the alkali metal hydroxide agent in the first stage is not critical. It can be added in several portions, for example, 2 to 4 portions, or continuously. The temperature in the first stage, at which the alkali metal hydroxide is contacted with the cellulose pulp, is typically in the range of 25 to 65°C, preferably in the range of 40 to 50°C. The first stage of alkalinization typically lasts for 15 to 60 minutes.

[0025] A methylating agent, such as methyl chloride or dimethyl sulfate, is also added to the cellulose pulp, typically after the addition of the alkali metal hydroxide. The total amount of methylating agent is generally 3 to 5.3 moles per mole of anhydroglucose units. The methylating agent can be added in a single stage or in two stages to the cellulose or partially reacted cellulose pulp as the reaction of the cellulose pulp to hydroxyalkylmethylcellulose progresses.

[0026] When the methylating agent is added in a single step, it generally reacts with the anhydroglucose unit 1 It is added in an amount of 3.4 to 5.3 moles of methylating agent per mole, but in any case it is added in an amount at least equimolar compared to the total molar amount of alkali metal hydroxide added before heating the reaction mixture.

[0027] If the methylating agent is added in two stages, in the first stage, it is generally added in an amount of 1.6 to 2.0 moles of methylating agent per mole of anhydroglucose unit before heating the reaction mixture, but in any case, it is added in an amount at least equimolar compared to the molar amount of alkali metal hydroxide added in the first stage of alkali metal hydroxide addition.

[0028] The methylating agent in the single stage or first stage may be premixed with the suspending agent. In this case, the mixture of suspending agent and methylating agent preferably contains 20 to 50 weight percent, more preferably 30 to 50 weight percent, of the suspending agent, based on the total weight of the methylating agent and suspending agent. After contacting the cellulose with the alkali metal hydroxide and methylating agent, the reaction temperature is typically raised to about 70 to 85°C, preferably about 75 to 80°C, over 30 to 45 minutes, and the reaction is continued at this temperature for 80 to 100 minutes.

[0029] When the methylating agent is added in two stages, the second stage methylating agent is generally added to the reaction mixture after heating the reaction mixture to a temperature of about 70-85°C for 10-30 minutes. The second stage methylating agent is generally added in an amount of 1.2-2.0 moles per mole of anhydroglucose units, but in any case, it is added in an amount at least equimolar compared to the molar amount of alkali metal hydroxide present in the reaction mixture. Thus, the second stage methylating agent, if present, is added to the reaction mixture before or after the second and, optionally, third stage alkali metal hydroxide additions, in such a manner that the alkali metal hydroxide does not come into contact with the cellulose pulp in excessive amounts. The second stage methylating agent is preferably added at a rate of 0.25-0.5 molar equivalents of methylating agent per mole of anhydroglucose units per minute. When the methylating agent is added in two stages, the molar ratio between the alkali metal hydroxide and the methylating agent in the first stage and the alkali metal hydroxide and the methylating agent in the second stage is generally 0.5:1 to 2:1.

[0030] When the alkali metal hydroxide is added in two stages, typically, 1.0 to 2.9 molar equivalents of alkali metal hydroxide per mole of anhydroglucose unit are added in the second stage, either in a single stage or after the addition of the methylating agent in the first stage, and simultaneously with or after the addition of the methylating agent in the second stage, if present. The molar ratio between the alkali metal hydroxide in the first stage and the alkali metal hydroxide in the second stage is generally 0.6:1 to 1.2:1. The alkali metal hydroxide in the second stage is generally added at a temperature of 55 to 80°C, preferably 60 to 80°C.

[0031] The pressure is then released from the reactor, which is nitrogen flushed to remove unreacted methylating agent.

[0032] Thereafter, one or more, preferably one or two, hydroxyalkylating agents such as ethylene oxide and / or propylene oxide are added to the reaction before, after, or simultaneously with the addition of the alkali metal hydroxide in the second or third stage. Preferably, only one hydroxyalkylating agent is used. The hydroxyalkylating agent is generally added in an amount of 0.5 to 2.0 moles of hydroxyalkylating agent per mole of anhydroglucose unit. The hydroxyalkylating agent is advantageously added before heating the reaction mixture to the reaction temperature, i.e., a temperature of 60 to 80°C.

[0033] The resulting hydroxyalkyl methylcellulose is purified by removing salts and other reaction by-products. The hydroxyalkyl methyl cellulose is washed to remove the residual organic matter. Any solvent in which the salt is soluble may be utilized, but water is preferred. The hydroxyalkyl methyl cellulose may be washed in the reactor, but is preferably washed in a separate washer located downstream of the reactor. Before or after washing, the hydroxyalkyl methyl cellulose may be stripped by exposure to steam to reduce the residual organic content.

[0034] The hydroxyalkyl methyl cellulose is dried to a reduced water and volatile content, preferably about 0.5 to about 10.0 weight percent water, more preferably about 0.8 to about 5.0 weight percent water and volatile content, based on the combined weight of the hydroxyalkyl methyl cellulose and volatile material. The reduction in water and volatile material content allows the hydroxyalkyl methyl cellulose to be milled into particulate form. The hydroxyalkyl methyl cellulose is milled into fine particles of the desired size. If desired, drying and milling can be performed simultaneously.

[0035] According to the above method, the shear rate was 2.51 s -1This typically results in a hydroxyalkyl methylcellulose having a viscosity of 150 mPa·s to 100,000 mPa·s, determined as a 2 wt. % aqueous solution at 20°C. To prepare a hydroxyalkyl methylcellulose particularly suitable for the manufacture of capsules or coatings for dosage forms, such a hydroxyalkyl methylcellulose is typically subjected to a partial decomposition polymerization process. Partial decomposition polymerization processes are well known in the art and are described, for example, in EP 1,141,029; EP 210,917; EP 1,423,433; and U.S. Pat. No. 4,316,982. Alternatively, partial decomposition polymerization can be achieved, for example, by the presence of oxygen or an oxidizing agent during the preparation of the hydroxyalkyl methylcellulose. In such a partial decomposition polymerization process, a hydroxyalkyl methylcellulose having a viscosity of 2 to 20 mPa·s, preferably 3 to 15 mPa·s, determined as a 20 wt. % aqueous solution at 20°C according to ASTM D2363-79 (reapproved 2006) can be obtained.

[0036] In one embodiment, the hydroxyalkyl methylcelluloses, particularly hydroxypropyl methylcelluloses, of the present invention may be useful for preparing solid food compositions that have greater hardness and / or cohesive strength than solid food compositions comprising comparable known hydroxyalkyl methylcelluloses, particularly hydroxypropyl methylcelluloses.

[0037] The hydroxyalkyl methylcellulose of the present invention is typically incorporated into food compositions at a level of 0.05 to 10 percent, preferably 0.1 to 8 percent, more preferably 0.2 to 5 percent, and most preferably 0.5 to 2 percent, based on the total weight of the food composition.

[0038] The hydroxyalkyl methylcellulose of the present invention is preferably incorporated into solid food compositions, particularly those designed to be heat-treated, such as frying, roasting, grilling, cooking, baking, or poaching. Preferred food compositions include vegetable, meat, fish, and soybean patties and balls, vegetable, meat, fish, and soybean sausages, extruded vegetable, meat, fish, and soybean products, modified seafood; modified cheese sticks; onion rings; pie fillings; pasta fillings; cooked and baked sweet and savory fillings; starch-based fried, grilled, roasted, cooked, baked, or poached products; meat analogs; extruded potato products, such as croquettes, pomme duchesse, hash browns, pancakes, waffles, and cakes; chewy snacks; pet food; and leavened or unleavened baked foods, such as bread. In a preferred embodiment of the present invention, the food composition is a proteinaceous food composition, in particular a proteinaceous vegetarian food product, such as soy sausages and patties, meatless meatballs, etc. and tofu turkey rolls.

[0039] In forming food compositions, hydroxyalkyl methylcellulose is typically mixed with food during processing and formation of the composition. The food compositions of the present invention can be frozen pre-formed or pre-cut products, uncooked premixes, or pre-formed or pre-cut cooked products, such as fried, roasted, grilled, cooked, or poached products. The hydroxyalkyl methylcellulose provides excellent stability of the food composition during and after cooking. The hydroxyalkyl methylcellulose may be the only cellulose ether contained in the food composition. Alternatively, one or more other cellulose ethers, such as those described in EP 1171471, can be incorporated into the food compositions of the present invention, preferably in an amount of 0.5 to 2 percent based on the total weight of the food composition.

[0040] In another embodiment, the hydroxyalkyl methyl cellulose of the present invention can be included in a composition for making an extruded ceramic body, the composition comprising an inorganic material that sets as a result of calcination or sintering, a hydroxyalkyl methyl cellulose as described herein, and water.

[0041] The inorganic ceramic-forming materials may be synthetically produced materials such as oxides or hydroxides, or may be naturally occurring minerals such as clays or talcs, or any combination thereof. More preferably, the inorganic material is alumina or its precursor, silica or its precursor, aluminate, aluminosilicate, alumina-silica, feldspar, titania, fused silica, aluminum nitride, aluminum carbide, kaolin, cordierite or its precursor, mullite or its precursor, clay, bentonite, talc, zircon, zirconia, spinel, silicon carbide, silicon boride, silicon nitride, titanium dioxide, titanium carbide, boron carbide, boron oxide, borosilicate, barium sodium borosilicate, silicates and layered silicates, silicon metal, carbon, powdered glass, rare earth oxides, soda lime, zeolite, barium titanate, lead titanate zirconate, aluminum titanate, barium ferrite, strontium ferrite, carbon, powdered glass, metal oxides such as rare earth oxides, or a combination of two or more of such inorganic materials. The term "clay" refers to hydrated aluminum silicate having a plate-like structure, which forms a plastic mass when mixed with water. Typically, clays are composed of one or more crystalline structures such as kaolin, illite, and smectite. Preferred oxides are those that form cordierite or mullite when mixed with the clay (e.g., silica and talc to form cordierite, and alumina to form mullite).

[0042] The composition for producing the extrudate preferably comprises 85 to 99.5 percent, more preferably 90 to 99.3 percent, and most preferably 92 to 99 percent inorganic material and 0.5 to 15 percent, more preferably 0.7 to 10 percent, and most preferably 1 to 8 percent hydroxyalkyl methyl cellulose, based on the combined weight of the inorganic material and hydroxyalkyl methyl cellulose.

[0043] The composition for producing the extrudate is preferably in paste form. It typically contains a diluent that is liquid at 25°C and provides a medium for dissolving the hydroxyalkyl methylcellulose, thereby imparting plasticity to the batch and wetting the powder. The liquid diluent may be aqueous, typically water or a water-miscible solvent, or organic, or a mixture thereof. Water is most preferred. The composition for producing the extrudate preferably contains 10 to 60 parts by weight, more preferably 20 to 50 parts by weight, and most preferably 15 to 40 parts by weight of the liquid diluent per 100 parts by weight of the inorganic material.

[0044] Uniform mixing of the inorganic material, hydroxyalkyl methylcellulose, typically a liquid diluent, and optional other additives, such as surfactants, lubricants, and pore-forming materials, can be achieved, for example, by known conventional kneading processes. The resulting extrudable composition for the extrudate is typically firm and uniform. It can then be formed into a green body by any known conventional ceramic extrusion process. In an exemplary embodiment, extrusion can be carried out using a hydraulic ram extrusion press, a two-stage degassing single-auger extruder, or a twin-screw extruder fitted with a die assembly at the discharge end. The produced green body can then be dried to remove excess moisture. Drying can be carried out by hot air drying, steam drying, or dielectric drying, which can be followed by air drying. After drying, the green body can then be fired under conditions effective to convert the green body into a sintered article according to known techniques. The firing temperature and time conditions depend on the composition and size and shape of the green body, and the present invention is not limited to specific firing temperatures and times. Typical temperatures are between 600°C and 2300°C, and hold times at these temperatures are typically between 1 and 20 hours.

[0045] The extruded bodies of the present invention can have any convenient size and shape. They are useful for many applications, such as catalyst supports, catalysts, heat exchangers, or filters, such as diesel particulate filters, molten metal filters, and regenerator cores. In a preferred embodiment, the compositions and methods of the present invention are well suited for the production of cellular structures, such as honeycombs. These cellular ceramic bodies are particularly useful as catalyst supports or catalytic filters for exhaust gas treatment.

[0046] Typically, honeycomb densities are around 15 cells / cm 2 ~approximately 235 cells / cm 2Typical wall thicknesses are in the range of 0.05 to 0.65 mm. However, it should be understood that the specific desired size and shape of the ceramic body may depend on the application, e.g., in automotive applications, the engine size and the space available for installation. While the extruded bodies of the present invention are, in one aspect, suitable for producing thin-walled honeycombs, the claimed mixtures may also be used for thicker-walled structures.

[0047] In a further embodiment, the present invention relates to an aqueous composition for producing capsules or coatings for dosage forms, comprising 7 to 40 weight percent, preferably 10 to 30 weight percent, of the hydroxyalkyl methylcellulose of the present invention, having a viscosity of 2 to 20 mPa·s, preferably 3 to 15 mPa·s, as determined as a 20 wt% aqueous solution at 20°C according to ASTM D2363-79 (reapproved 2006). The aqueous composition may further contain optional additives such as colorants, flavor and taste improvers, antioxidants, plasticizers, and surfactants. For example, when producing capsules, water-soluble food dyes such as red iron oxide or natural dyes can be used as colorants; TiO can be used as a masking agent; and polyethylene glycol, polypropylene glycol, sorbitol, or glycerin can be used as plasticizers or surfactants to improve the flexibility of the capsule film. Additives that are particularly useful for solid form coatings are monolayer film plasticizers, solids loading promoters, second cellulose ethers, surfactants, lubricants, abrasives, pigments, antiblocking agents, glidants, opacifying agents, colorants, and any combination thereof.

[0048] The aqueous composition can be used to coat dosage forms, such as tablets, granules, pellets, caplets, lozenges, suppositories, pessaries, or implantable dosage forms, to form a coated composition. Preferred dosage forms are pharmaceutical dosage forms, nutritional supplements, or agricultural dosage forms.

[0049] Furthermore, the aqueous composition can be used for the manufacture of capsules. One method for this is the "hot pin method", which preferably includes the steps of: (a) preparing an aqueous composition containing the above-mentioned low-viscosity hydroxyalkyl methylcellulose and optional additives; (b) preheating a dip pin so that when immersed in the aqueous composition, the temperature will be higher than the gelling temperature of the aqueous composition; (c) immersing the preheated dip pin in the aqueous composition maintained at a temperature below the gelling temperature; (d) withdrawing the dip pin from the aqueous composition to obtain a film on the dip pin; and (e) drying the film on the dip pin at a temperature above the gelling temperature of the aqueous composition to obtain a capsule shell formed on the pin.

[0050] In this hot pin method, the dip pin is preferably preheated so that the temperature when immersed in the aqueous composition is 55 to 95°C, preferably 60 to 90°C. The preheated dip pin is immersed in the aqueous composition, which is preferably maintained at a temperature 10 to 1°C, more preferably 4 to 1°C lower than the gelling temperature of the aqueous composition. The hot pin method used to produce capsules from aqueous compositions of hydroxyalkyl methylcellulose is described in detail in International Patent Application Publication WO 2008 / 050209. [Example]

[0051] The following examples are provided for illustrative purposes only and are not intended to limit the scope of the present invention. All percentages are by weight unless otherwise specified.

[0052] Measurement of % methoxyl and % hydroxypropoxy in hydroxypropyl methylcellulose is performed according to the United States Pharmacopoeia (USP 32). The values ​​obtained are % methoxyl and % hydroxypropoxy. These are then converted to degree of substitution (DS) for the methyl substituent and molar substitution (MS) for the hydroxypropyl substituent. Residual amounts of salts were taken into account in the conversion.

[0053] The DS (methyl) and MS (hydroxyethyl) forms of hydroxyethyl methylcellulose are separated by Zeisel cleavage with hydrogen iodide followed by gas chromatography (G. Bartelmus and R. Ketterer, Z. Anal. Chem. 286; 1977: 161-190).

[0054] Decision of s23 / s26 The determination of the ether substituents in cellulose ethers is generally known and is described, for example, in Bengt Lindberg, Ulf Lindquist, and Olle Stenberg, Carbohydrate Research, 176 (1988) 137-144, Elsevier Science Publishers BV, Amsterdam, DISTRIBUTION OF SUBSTITUENTS IN O-ETHYL-O-(2-HYDROXYETHYL) CELLULOSE.

[0055] Specifically, the determination of s23 / s26 is carried out as follows: 10-12 mg of cellulose ether is dissolved in 4.0 mL of dry, analytical-grade dimethyl sulfoxide (DMSO) (Merck, Darmstadt, Germany, stored on 0.3 nm molecular sieve beads) under stirring at approximately 90 °C, then cooled again to room temperature. To ensure complete solubilization, the solution is left stirring overnight at room temperature. All reactions, including the solubilization of cellulose ether, are carried out in 4 mL screw-cap vials using a dry nitrogen atmosphere. After solubilization, the dissolved cellulose ether is transferred into a 22 mL screw-cap vial. Powdered sodium hydroxide (freshly ground with a pestle, analytical grade, Merck) is dissolved in a 30-fold molar excess of the reagents sodium hydroxide and ethyl iodide per hydroxyl group of the anhydroglucose unit. ck, Darmstadt, Germany) and ethyl iodide (analytical grade, silver stabilized, Merck-Schuchardt, Hohenbrunn, Germany) are added, and the solution is vigorously stirred under nitrogen in the dark at ambient temperature for 3 days. The perethylation is repeated by adding three times the amount of reagents sodium hydroxide and ethyl iodide compared to the initial reagent addition and stirring for another 2 days at room temperature.

[0056] To ensure good mixing during the course of the reaction, the reaction mixture can optionally be diluted with up to 1.5 mL of DMSO. Five mL of 5% aqueous sodium thiosulfate solution is poured into the reaction mixture, and the resulting solution is then extracted three times with 4 mL of dichloromethane. The combined extracts are washed three times with 2 mL of water. The organic phase is dried with anhydrous sodium sulfate (approximately 1 g). After filtration, the solvent is removed in a gentle stream of nitrogen, and the sample is stored at 4 °C until further sample preparation.

[0057] Hydrolysis of approximately 5 mg of perethylated sample is carried out under nitrogen in a 2 mL screw-cap vial containing 1 mL of 90% aqueous formic acid at 100 °C for 1 h with stirring. The acid is removed in a nitrogen stream at 35-40 °C, and the hydrolysis is repeated with 1 mL of 2 M aqueous trifluoroacetic acid at 120 °C for 3 h with stirring in an inert nitrogen atmosphere. After completion, the acid is removed to dryness in a nitrogen stream at ambient temperature, using approximately 1 mL of toluene for co-distillation. The hydrolysis residue is reduced with 0.5 mL of 0.5 M sodium borodeuteride in 2 N aqueous ammonia (freshly prepared) for 3 h at room temperature with stirring. Excess reagent is destroyed by the dropwise addition of approximately 200 μL of concentrated acetic acid. The resulting solution is evaporated to dryness in a nitrogen stream at approximately 35-40 °C, followed by drying in vacuo at room temperature for 15 min. The viscous residue is dissolved in 0.5 mL of 15% acetic acid in methanol and evaporated to dryness at room temperature. This is done five times, and repeated four times with pure methanol. After the final evaporation, the samples are dried in vacuo at room temperature overnight.

[0058] The residue from the reduction is acetylated with 600 μL of acetic anhydride and 150 μL of pyridine at 90° C. for 3 hours. After cooling, a sample vial is filled with toluene and evaporated to dryness in a nitrogen stream at room temperature. The residue is dissolved in 4 mL of dichloromethane, poured into 2 mL of water, and extracted with 2 mL of dichloromethane. The extraction is repeated three times. The combined extracts are washed three times with 4 mL of water and dried using anhydrous sodium sulfate. The dried dichloromethane extract is then subjected to GC analysis. Depending on the sensitivity of the GC system, further dilution of the extract may be necessary.

[0059] Gas-liquid (GLC) chromatography analysis was performed using a Hewlett Packard 5890A and 5890A Series II gas chromatograph equipped with a J&W DB5 capillary column, 30 m, 0.25 mm internal diameter, and 0.25 μm total phase thickness, operated with 1.5 bar helium carrier gas. The gas chromatograph was programmed with a temperature profile that held constant at 60°C for 1 minute, heated to 200°C at 20°C / min, further heated to 250°C at 4°C / min, further heated to 310°C at 20°C / min, and held constant for an additional 10 minutes. The injector temperature was set to 280°C, and the flame ionization detector (FID) temperature was set to 300°C. 1 mL samples were injected in splitless mode with a valve time of 0.5 minutes. Data were acquired and processed by a LabSystems Atlas workstation.

[0060] Quantitative monomer composition data are obtained from peak areas measured by GLC with FID detection. The molar response of the monomers is calculated according to the modified effective carbon number (ECN) concept as described in the table below. The effective carbon number (ECN) concept was developed by Ackman (R.G. Ackman, J. Gas Chromatogr., 2 (1964) 17 3-179 and RF Addison, R.G. Backman, J. Gas Chromatogr., 6 (1968) 135-138) and was applied to the quantitative analysis of partially alkylated alditol acetates by Sweet et al. (D.P. Sweet, R.H. Shapiro, P. Albersheim, Carbohy. Res., 40 (1975) 217-225).

[0061] [Table 1]

[0062] To correct for the different molar responses of the monomers, the peak area is multiplied by the molar response factor MRFmonomer, defined as the response to the 2,3,6-Me monomer. The 2,3,6-Me monomer is chosen as the reference because it is present in all samples analyzed in the determination of s23 / s26. MRF monomer = ECN2,3,6-Me / ECN monomer The mole fraction of the monomer is calculated by the following formula: s23=[(23-Me+23-Me-6-HAMe+23-Me-6-HA+23-Me-6-HAHAMe+23-Me-6-HAHA]; and s26=[(26-Me+26-Me-3-HAMe+26-Me-3-HA+26-Me-3-HAHAMe+26-Me-3-HAHA] where s23 is the sum of the mole fractions of anhydroglucose units that satisfy the following condition: a) The two hydroxy groups at positions 2 and 3 of the anhydroglucose unit are substituted with methyl groups, and the 6 position is unsubstituted (=23-Me); b) the two hydroxy groups at positions 2 and 3 of the anhydroglucose unit are substituted with methyl groups, and position 6 is substituted by a methylated hydroxyalkyl (=23-Me-6-HAMe) or by a methylated side chain containing two hydroxyalkyl groups (=23-Me-6-HAHAMe); and c) The two hydroxy groups at positions 2 and 3 of the anhydroglucose unit are substituted with methyl groups, and position 6 is substituted by a hydroxyalkyl group (=23-Me-6-HA) or by a side chain containing two hydroxyalkyl groups (=23-Me-6-HAHA). s26 is the sum of the mole fractions of anhydroglucose units that satisfy the following condition: a) The two hydroxy groups at positions 2 and 6 of the anhydroglucose unit are substituted with methyl groups, and the 3 position is unsubstituted (=26-Me); b) the two hydroxy groups at positions 2 and 6 of the anhydroglucose unit are substituted with methyl groups, and position 3 is substituted by a methylated hydroxyalkyl (=26-Me-3-HAMe) or by a methylated side chain containing two hydroxyalkyl groups (=26-Me-3-HAHAMe); and c) The two hydroxy groups at positions 2 and 6 of the anhydroglucose unit are substituted with methyl groups, and the 3 position is substituted by a hydroxyalkyl (=26-Me-3-HA) or by a side chain containing two hydroxyalkyl groups (=26-M e-3-HAHA). The results of the determination of the substituents of HAMC are listed below in Table 4. In the case of hydroxyalkyl (HA) of HPMC, it is hydroxypropyl (HP) and methylated hydroxyalkyl (HAMe) is methylated hydroxypropyl (HPMe).

[0063] Example 1 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is loaded into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose at 3.5 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 2 moles of dimethyl ether and 3.9 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 90 minutes, after which it is cooled to 70°C. The pressure in the reactor is then released, the reactor is purged twice with nitrogen, and the reactor is depressurized to a final pressure of 5 bar at 70°C.

[0064] The second stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 1.2 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0065] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0066] The resulting HPMC had a DS (methyl) of 1.67, an MS (hydroxypropyl) of 0.11, an s23 / s26 (methyl) of 0.416, and an s6 (hydroxypropyl) of 0.037.

[0067] Example 2 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is loaded into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose at 3.7 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 2 moles of dimethyl ether and 4.1 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 90 minutes, after which it is cooled to 70°C. The pressure in the reactor is then released, the reactor is purged twice with nitrogen, and the reactor is depressurized to a final pressure of 5 bar at 70°C.

[0068] The second stage of the reaction was the addition of 50 wt. % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 1.2 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes. The reactor contents were then heated to 80° C. in 10 minutes, after which the reactor contents were held at a temperature of 80° C. for 45 minutes.

[0069] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0070] The resulting HPMC had a DS (methyl) of 1.71, an MS (hydroxypropyl) of 0.09, an s23 / s26 (methyl) of 0.399, and an s6 (hydroxypropyl) of 0.031.

[0071] Example 3 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is loaded into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose at 3.9 moles of sodium hydroxide per mole of anhydroglucose unit in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 2 moles of dimethyl ether and 4.3 moles of methyl chloride per mole of anhydroglucose unit are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 90 minutes, after which it is cooled to 70°C. The pressure in the reactor is then released, the reactor is purged twice with nitrogen, and the reactor is depressurized to a final pressure of 5 bar at 70°C.

[0072] The second stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 1.2 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0073] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0074] The resulting HPMC had a DS (methyl) of 1.75, an MS (hydroxypropyl) of 0.08, an s23 / s26 (methyl) of 0.465, and an s6 (hydroxypropyl) of 0.027.

[0075] Example 4 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure: Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 3.5 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. The mixture of aqueous sodium hydroxide and cellulose is stirred at 40°C for about 30 minutes, after which 2 moles of sodium hydroxide per mole of anhydroglucose units are added. Dimethyl ether and 3.9 moles of methyl chloride are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first stage reaction is allowed to proceed for 90 minutes, after which it is cooled to 70°C. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen and reduced pressure to a final pressure of 5 bar at 70°C.

[0076] The second stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 0.8 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0077] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0078] The resulting HPMC had a DS (methyl) of 1.67, an MS (hydroxypropyl) of 0.07, an s23 / s26 (methyl) of 0.417, and an s6 (hydroxypropyl) of 0.027.

[0079] Example 5 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is loaded into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose at 3.9 moles of sodium hydroxide per mole of anhydroglucose unit in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 2 moles of dimethyl ether and 4.3 moles of methyl chloride per mole of anhydroglucose unit are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 90 minutes, after which it is cooled to 70°C. The pressure in the reactor is then released, the reactor is purged twice with nitrogen, and the reactor is depressurized to a final pressure of 5 bar at 70°C.

[0080] The second stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 0.8 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0081] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0082] The resulting HPMC had a DS (methyl) of 1.76, an MS (hydroxypropyl) of 0.05, an s23 / s26 (methyl) of 0.406, and an s6 (hydroxypropyl) of 0.018.

[0083] Example 6 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is loaded into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose at 2.8 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 2 moles of dimethyl ether and 3.2 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 70°C over 35 minutes. After reaching 70°C, the first-stage reaction is allowed to proceed for 90 minutes. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen.

[0084] The second stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 1.3 moles of sodium hydroxide per mole of anhydroglucose unit, which was allowed to react for 10 minutes at 70° C., followed by the addition of propylene oxide over 10 minutes in an amount of 1.0 mole of propylene oxide per mole of anhydroglucose unit, after which the reactor contents were held at a temperature of 70° C. for 40 minutes.

[0085] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0086] The resulting HPMC had a DS (methyl) of 1.19, an MS (hydroxypropyl) of 0.21, an s23 / s26 (methyl) of 0.484, and an s6 (hydroxypropyl) of 0.066.

[0087] Example 7 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is loaded into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose at 3.5 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 2 moles of dimethyl ether and 3.9 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 70°C over 35 minutes. After reaching 70°C, the first-stage reaction is allowed to proceed for 90 minutes. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen.

[0088] The second stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 1.3 moles of sodium hydroxide per mole of anhydroglucose unit, which was allowed to react for 10 minutes at 70° C., followed by the addition of propylene oxide over 10 minutes in an amount of 1.0 mole of propylene oxide per mole of anhydroglucose unit, after which the reactor contents were held at a temperature of 70° C. for 40 minutes.

[0089] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred to a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air sweep dryer at 55°C. The material is then filtered through a 0.5 mm screen. The powder is ground using an Alpine UPZ mill.

[0090] The resulting HPMC had a DS (methyl) of 1.3, an MS (hydroxypropyl) of 0.16, an s23 / s26 (methyl) of 0.475, and an s6 (hydroxypropyl) of 0.05.

[0091] Example 8 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.2 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 1.6 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 60°C over 15 minutes.

[0092] The second stage of the reaction is initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and methyl chloride in an amount of 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents are then heated to 80°C in 20 minutes, held at 80°C for 30 minutes, and subsequently cooled to 70°C. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen and reduced pressure to a final pressure of 5 bar at 70°C.

[0093] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 0.8 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0094] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0095] The resulting HPMC had a DS (methyl) of 1.26, an MS (hydroxypropyl) of 0.17, an s23 / s26 (methyl) of 0.469, and an s6 (hydroxypropyl) of 0.055.

[0096] Example 9 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure: Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.4 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. The mixture of aqueous sodium hydroxide and cellulose is stirred at 40°C for about 30 minutes, after which 1.5 moles of dimethyl ether and 1.8 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor is then cooled to 40°C. The contents are heated to 80° C. in 35 minutes. After reaching 80° C., the first stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 60° C. in 15 minutes.

[0097] The second stage of the reaction is initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and methyl chloride in an amount of 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents are then heated to 80°C in 20 minutes, held at 80°C for 30 minutes, and subsequently cooled to 70°C. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen and reduced pressure to a final pressure of 5 bar at 70°C.

[0098] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 0.8 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0099] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0100] The resulting HPMC had a DS (methyl) of 1.37, an MS (hydroxypropyl) of 0.14, an s23 / s26 (methyl) of 0.446, and an s6 (hydroxypropyl) of 0.042.

[0101] Example 10 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.6 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 2.0 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 60°C over 15 minutes.

[0102] The second stage of the reaction is initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and methyl chloride in an amount of 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents are then heated to 80°C in 20 minutes, held at 80°C for 30 minutes, and subsequently cooled to 70°C. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen and reduced pressure to a final pressure of 5 bar at 70°C.

[0103] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 0.8 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0104] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0105] The resulting HPMC had a DS (methyl) of 1.52, an MS (hydroxypropyl) of 0.12, an s23 / s26 (methyl) of 0.418, and an s6 (hydroxypropyl) of 0.051.

[0106] Example 11 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.2 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 1.6 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 60°C over 15 minutes.

[0107] The second stage of the reaction is initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and methyl chloride in an amount of 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents are then heated to 80°C in 20 minutes, held at 80°C for 30 minutes, and subsequently cooled to 70°C. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen and reduced pressure to a final pressure of 5 bar at 70°C.

[0108] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 1.2 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0109] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0110] The resulting HPMC had a DS (methyl) of 1.22, an MS (hydroxypropyl) of 0.26, an s23 / s26 (methyl) of 0.437, and an s6 (hydroxypropyl) of 0.072.

[0111] Example 12 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure: Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction proceeds in two stages: In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.6 moles of sodium hydroxide per mole of anhydroglucose unit in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 2.0 moles of methyl chloride per mole of anhydroglucose unit are added to the reactor. The contents of the reactor are then heated to 80°C over 35 minutes. After reaching 80°C, the first stage reaction is allowed to proceed for 15 minutes, and the contents of the reactor are cooled to 60°C over 15 minutes.

[0112] The second stage of the reaction is initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and methyl chloride in an amount of 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents are then heated to 80°C in 20 minutes, held at 80°C for 30 minutes, and subsequently cooled to 70°C. The pressure in the reactor is then released, and the reactor is purged twice with nitrogen and reduced pressure to a final pressure of 5 bar at 70°C.

[0113] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 0.5 moles of sodium hydroxide per mole of anhydroglucose unit and propylene oxide in an amount of 1.2 moles of propylene oxide per mole of anhydroglucose unit over a period of 10 minutes, and then the reactor contents were heated to 80°C in 10 minutes, after which the reactor contents were held at a temperature of 80°C for 45 minutes.

[0114] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0115] The resulting HPMC had a DS (methyl) of 1.49, an MS (hydroxypropyl) of 0.18, an s23 / s26 (methyl) of 0.429, and an s6 (hydroxypropyl) of 0.039.

[0116] Example 13 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.2 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 1.6 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 70°C over 15 minutes.

[0117] The second stage of the reaction was initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.2 moles of sodium hydroxide per mole of anhydroglucose unit and methyl chloride in an amount of 1.44 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents were then heated to 80°C in 18 minutes, held at 80°C for 26 minutes, and subsequently cooled to 70°C. The pressure in the reactor was then released, and the reactor was purged with nitrogen three times at 70°C.

[0118] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 1.3 moles of sodium hydroxide per mole of anhydroglucose unit, which was allowed to react for 10 minutes at 70° C., followed by the addition of propylene oxide over 10 minutes in an amount of 1.0 mole of propylene oxide per mole of anhydroglucose unit, after which the reactor contents were held at a temperature of 70° C. for 40 minutes.

[0119] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0120] The resulting HPMC had a DS (methyl) of 1.18, an MS (hydroxypropyl) of 0.24, an s23 / s26 (methyl) of 0.385, and an s6 (hydroxypropyl) of 0.075.

[0121] Example 14 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 2.0 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 70°C over 15 minutes.

[0122] The second stage of the reaction was initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents were then heated to 80°C in 18 minutes, held at 80°C for 16 minutes, and subsequently cooled to 70°C. The pressure in the reactor was then released, and the reactor was purged with nitrogen three times at 70°C.

[0123] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 1.3 moles of sodium hydroxide per mole of anhydroglucose unit, which was allowed to react for 10 minutes at 70° C., followed by the addition of propylene oxide over 10 minutes in an amount of 0.9 moles of propylene oxide per mole of anhydroglucose unit, after which the reactor contents were held at a temperature of 70° C. for 40 minutes.

[0124] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0125] The resulting HPMC had a DS (methyl) of 1.47, an MS (hydroxypropyl) of 0.14, an s23 / s26 (methyl) of 0.385, and an s6 (hydroxypropyl) of 0.046.

[0126] Example 15 Hydroxypropyl methylcellulose (HPMC) is produced according to the following procedure. Finely milled wood cellulose pulp is charged into a jacketed, stirred reactor. The reactor is evacuated to remove oxygen, purged with nitrogen, and then evacuated again. The reaction is carried out in two stages. In the first stage, 50 weight percent aqueous sodium hydroxide is sprayed onto the cellulose in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose units in the cellulose, and the temperature is adjusted to 40°C. After stirring the mixture of aqueous sodium hydroxide and cellulose at 40°C for approximately 30 minutes, 1.5 moles of dimethyl ether and 2.0 moles of methyl chloride per mole of anhydroglucose units are added to the reactor. The reactor contents are then heated to 80°C over 35 minutes. After reaching 80°C, the first-stage reaction is allowed to proceed for 15 minutes, and the reactor contents are cooled to 70°C over 15 minutes.

[0127] The second stage of the reaction was initiated by adding 50 wt. % aqueous sodium hydroxide in an amount of 1.5 moles of sodium hydroxide per mole of anhydroglucose unit and 1.8 molar equivalents of methyl chloride per mole of anhydroglucose unit. The reactor contents were then heated to 80°C in 18 minutes, held at 80°C for 26 minutes, and subsequently cooled to 70°C. The pressure in the reactor was then released, and the reactor was purged with nitrogen three times at 70°C.

[0128] The third stage of the reaction was initiated by adding 50 wt % aqueous sodium hydroxide in an amount of 1.3 moles of sodium hydroxide per mole of anhydroglucose unit, which was allowed to react for 10 minutes at 70° C., followed by the addition of propylene oxide over 10 minutes in an amount of 0.9 moles of propylene oxide per mole of anhydroglucose unit, after which the reactor contents were held at a temperature of 70° C. for 40 minutes.

[0129] After the reaction, the reactor is opened and cooled to 50°C. The reactor contents are removed and transferred into a tank containing hot water. The crude HPMC is then neutralized with formic acid, washed with hot water until chloride-free (as assessed by the AgNO3 agglomeration test), cooled to room temperature, and dried in an air-swept dryer at 55°C. The material is then ground using an Alpine UPZ mill using a 0.5 mm screen.

[0130] The resulting HPMC had a DS (methyl) of 1.49, an MS (hydroxypropyl) of 0.13, an s23 / s26 (methyl) of 0.363, and an s6 (hydroxypropyl) of 0.043.

[0131] Example 16 Determination of viscosity of aqueous solutions of HPMC of the present invention To obtain a homogeneous solution, 4 g of HPMC powder (taking into account the water content of HPMC) is suspended in 196 g of water at 70 °C using a laboratory overhead stirrer at 700 rpm for 10 minutes. These solutions are then cooled to a temperature below 5 °C for 2 hours to complete the dissolution process. During these 2 hours, the solutions are stirred at 500-1000 rpm to replenish the water lost through evaporation. These solutions are then stored in the refrigerator overnight.

[0132] The viscosity of hydroxypropyl methylcellulose was measured using an Anton Paar Physica MCR501 rheometer with a cup and bob geometry (CC-27) at 20°C and a shear rate of 2.51 s -1 and determined in a 2% by weight aqueous solution at 20°C.

[0133] Determination of storage modulus G', loss modulus G'', gelation temperature t, and gel strength To characterize the temperature dependence of gelation of 2 wt% aqueous solutions of cellulose ethers, An Anton Paar Physica MCR501 rheometer (Ostfildern, Germany) equipped with a tip-and-bob configuration (CC-27) and a Peltier temperature control system is used for oscillatory shear flow. These solutions are prepared by the same dissolution procedure described for viscosity measurements. Measurements are performed at a heating rate of 1 °C / min, a data collection rate of 4 points / min, a constant frequency of 2 Hz, and a constant strain (deformation amplitude) of 0.5% from 10 °C to 85 °C. The storage modulus G' obtained from the oscillatory measurements represents the elastic properties of the solution. The loss modulus G'' obtained from the oscillatory measurements represents the viscous properties of the solution. At low temperatures, the loss modulus value G'' is higher than the storage modulus G'. As the temperature increases, the storage modulus value increases, and the intersection of the storage and loss moduli is obtained. The intersection of G' and G'' is determined to be the gelation temperature.

[0134] The viscosity, gel temperature, and storage modulus G' of Examples 1 to 15 are shown in Table 1 below.

[0135] [Table 2]

[0136] [Table 3]

Claims

1. A hydroxyalkyl methylcellulose, wherein the substitution pattern of hydroxyalkyl groups in the anhydroglucose units of the hydroxyalkyl methylcellulose is such that s6 (hydroxyalkyl) is 0.01 to 0.1, s6 is the molar fraction of the anhydroglucose units in which the hydroxy group at the 6-position of the anhydroglucose unit is substituted with a hydroxyalkyl, the substitution pattern of methoxyl groups in the anhydroglucose units of the hydroxyalkyl methylcellulose is such that the s23 / s26 (methyl) ratio is 0.36 to 0.60, s23 is the molar fraction of the anhydroglucose units in which only the hydroxy groups at the 2- and 3-positions of the anhydroglucose unit are substituted with methyl, and s26 is the molar fraction of the anhydroglucose units in which only the hydroxy groups at the 2- and 6-positions of the anhydroglucose unit are substituted with methyl.

2. Temperature: 20°C and shear rate: 2.51 s －１ 2. The hydroxyalkyl methylcellulose of claim 1, having a viscosity of 150 mPa.s to 100,000 mPa.s, determined as a 2% by weight aqueous solution at 200°C.

3. 3. The hydroxyalkyl methylcellulose according to claim 1 or 2, having a gelation temperature in the range of 55 to 85°C, wherein the gelation temperature is a temperature at which G' / G" = 1, G' being the storage modulus of a 2 wt% aqueous solution of the hydroxypropyl methylcellulose, and G" being the loss modulus.

4. 4. The hydroxyalkyl methylcellulose according to any one of claims 1 to 3, having a storage modulus G' measured at 85°C as a 2 wt% aqueous solution in the range of 10 to 10,000 Pa, such as 12 to 9,500 Pa, for example 14 to 9,000 Pa, for example 16 to 8,500 Pa, such as 18 to 8,000 Pa, for example 20 to 7,500 Pa, such as 23 to 7,000 Pa, for example 25 to 7,000 Pa, such as 20 to 5,000 Pa, for example 25 to 5,000 Pa, such as 30 to 5,000 Pa, for example 40 to 5,000 Pa, such as 50 to 5,000 Pa, for example 60 to 5,000 Pa, such as 70 to 5,000 Pa, for example 80 to 5,000 Pa, or for example 90 to 5,000 Pa.

5. 5. The hydroxyalkyl methyl cellulose according to claim 1, wherein gelation occurs within a temperature interval of 10°C and is expressed as an increase in storage modulus G' of at least 5 times at the crossover of G' = G" within a temperature interval of 10°C.

6. 6. The hydroxyalkyl methyl cellulose according to any one of claims 1 to 5, having a DS of 1.0 to 2.0 and an MS of 0.05 to 0.5, wherein DS is the average number of hydroxyl groups substituted by methoxyl groups per anhydroglucose unit and MS is the average number of moles of hydroxyalkoxyl groups per anhydroglucose unit.

7. 7. The hydroxyalkyl methyl cellulose according to claim 6, having a DS of 1.2 to 1.8 and an MS of 0.1 to 0.3, wherein DS is the average number of hydroxyl groups replaced by methoxyl groups per anhydroglucose unit and MS is the average number of moles of hydroxyalkoxyl groups per anhydroglucose unit.

8. The substitution pattern of the methoxyl groups of the anhydroglucose units of the hydroxyalkylmethylcellulose is such that the s23 / s26 (methyl) ratio is 0.40 to 0.48 wherein s23 is the molar fraction of the anhydroglucose unit in which only the hydroxy groups at the 2- and 3-positions of the anhydroglucose unit are substituted with methyl, and s26 is the molar fraction of the anhydroglucose unit in which only the hydroxy groups at the 2- and 6-positions of the anhydroglucose unit are substituted with methyl. The hydroxyalkyl methylcellulose according to any one of claims 1 to 7,

9. The hydroxyalkyl methylcellulose according to any one of claims 1 to 8, wherein the substitution pattern of the hydroxyalkyl groups of the anhydroglucose units of the hydroxyalkyl methylcellulose is such that the s6 (hydroxyalkyl) is 0.04 to 0.06, and s6 is the molar fraction of the anhydroglucose units in which the hydroxy group at the 6-position of the anhydroglucose units of the hydroxyalkyl methylcellulose is substituted with a hydroxyalkyl.

10. The hydroxyalkyl methylcellulose according to any one of claims 1 to 9, which is hydroxypropyl methylcellulose.

11. A composition for producing an extruded ceramic body, comprising an inorganic material that solidifies as a result of firing or sintering, the hydroxyalkyl methyl cellulose of any one of claims 1 to 9, and water.

12. A solid food composition designed to be heat-treated, comprising the hydroxyalkyl methylcellulose of any one of claims 1 to 9.

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