05572M2K90

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A diclofenac submicron cream was prepared as follows: Oil phase--diclofenac diethylammonium 12.2 g, MCT oil 170 g, LIPOID E-80 30 g, α-tocopherol succinate 0.4 g; Aqueous phase--EDTA disodium salt 1 g, EMULFOR EL-620 25 g, glycerol 17.5 g, preservatives (methyl and propyl parabens) 0.5 g, reverse osmosis purified water to 1000 g. purified water to 1000 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 50 ml of dioxane, 20.00 g of polyethylene glycol monooleyl ether (average molecular weight 4,268) obtained by addition of ethylene oxide to an oleyl alcohol in the presence of an alkali catalyst and 1.90 g of triethyl amine were dissolved. The resultant solution and a solution of 1.85 g of p-toluenesulfonyl chloride in 10 ml of dioxane slowly added dropwise thereto were left reacting at 60° C. for two hours. The reaction product was refined by being dissolved with 200 ml of acetone added thereto, then cooled to 0° C., and left standing to allow sedimentation of the product aimed at. Then, a solution of 6.50 g of the product mentioned above in 30 ml of DMF and 0.55 g of potassium phthalimide added thereto were left reacting at 90° C. for two hours. The reaction product was refined by being dissolved with 60 ml of acetone added thereto, then cooled to 0° C., and left standing to allow sedimentation of the product aimed at. Subsequently, a solution of 6.00 g of the product mentioned above in 30 ml of ethanol and 1.00 g of hydrazinc hydrate added thereto were left reacting as refluxed for two hours. The reaction product was refined by being dissolved with 60 ml of acetone added thereto, then cooled to 0° C., and left standing to allow sedimentation of the product aimed at. Consequently, 5.20 g of an oleyl alcohol macromer possessed of amino groups at the terminals thereof was obtained.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Surface-active dispersing agents in the form of oxyalkylated esters of unsaturated higher fatty acids are preferred. Oxymethylated and/or oxyethylated esters are especially preferred. In this, case, a glyceride type ester is preferred. This ester can be a mono-, di- and tri-glyceride. The oxyalkylated forms of the esters which can be used in accordance with the invention are obtained, in particular, from esters of unsaturated higher fatty acids which can undergo an oxyalkylation, particularly an oxyethylation. Particularly useful fatty acids are oleic acid, elaidic acid, linoleic acid and ricinoleic acid. The oxyethylated glyceride of ricinoleic acid, which can be advantageously used in the form of ethoxylated castor oil is of particular value for the purposes of the present invention. Castor oil consists of 80 to 85% of the glyceride of ricinoleic acid, and in addition the glycerides of oleic (7%), linoleic (3%), palmitic (2%) and stearic (1%) acids. Ethoxylated castor oil is marked by a good solubility in fatty acids, polar solutions and water. The oxyethylated castor oil may be that produced commercially by BASF (trademark: Emulphor EL). This castor oil is a yellow oil, having a freezing point below +20° C., and which is soluble in fatty acids, waxes, castor oil, polar solvents (e.g., trichloroethylene, xylene) and water. are obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Surface-active dispersing agents in the form of oxyalkylated esters of unsaturated higher fatty acids are preferred. Oxymethylated and/or oxyethylated esters are especially preferred. In this, case, a glyceride type ester is preferred. This ester can be a mono-, di- and tri-glyceride. The oxyalkylated forms of the esters which can be used in accordance with the invention are obtained, in particular, from esters of unsaturated higher fatty acids which can undergo an oxyalkylation, particularly an oxyethylation. Particularly useful fatty acids are oleic acid, elaidic acid, linoleic acid and ricinoleic acid. The oxyethylated glyceride of ricinoleic acid, which can be advantageously used in the form of ethoxylated castor oil is of particular value for the purposes of the present invention. Castor oil consists of 80 to 85% of the glyceride of ricinoleic acid, and in addition the glycerides of oleic (7%), linoleic (3%), palmitic (2%) and stearic (1%) acids. Ethoxylated castor oil is marked by a good solubility in fatty acids, polar solutions and water. The oxyethylated castor oil may be that produced commercially by BASF (trademark: Emulphor EL). This castor oil is a yellow oil, having a freezing point below +20° C., and which is soluble in fatty acids, waxes, castor oil, polar solvents (e.g., trichloroethylene, xylene) and water. are obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Surface-active dispersing agents in the form of oxyalkylated esters of unsaturated higher fatty acids are preferred. Oxymethylated and/or oxyethylated esters are especially preferred. In this, case, a glyceride type ester is preferred. This ester can be a mono-, di- and tri-glyceride. The oxyalkylated forms of the esters which can be used in accordance with the invention are obtained, in particular, from esters of unsaturated higher fatty acids which can undergo an oxyalkylation, particularly an oxyethylation. Particularly useful fatty acids are oleic acid, elaidic acid, linoleic acid and ricinoleic acid. The oxyethylated glyceride of ricinoleic acid, which can be advantageously used in the form of ethoxylated castor oil is of particular value for the purposes of the present invention. Castor oil consists of 80 to 85% of the glyceride of ricinoleic acid, and in addition the glycerides of oleic (7%), linoleic (3%), palmitic (2%) and stearic (1%) acids. Ethoxylated castor oil is marked by a good solubility in fatty acids, polar solutions and water. The oxyethylated castor oil may be that produced commercially by BASF (trademark: Emulphor EL). This castor oil is a yellow oil, having a freezing point below +20° C., and which is soluble in fatty acids, waxes, castor oil, polar solvents (e.g., trichloroethylene, xylene) and water. are obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Firstly, 35 g of dimethylacrylamide (manufactured by Kojin Co., Ltd.), 17.5 g of 2-acrylamido-2-methylpropanesulfonic acid (manufactured by Sigma), and 7 mg of methylenebisacrylamide were dissolved in ion-exchanged water, and the pH value of the resulting solution was adjusted at 7.0 by the addition of sodium hydroxide. Thereafter, 260 g of n-hexane, 8.7 g of polyoxyethylene (3) oleyl ether (EMULEX 503, manufactured by Nihon Emulsion Co., Ltd.), and 17.6 g of polyoxyethylene (6) oleyl ether (EMULEX 506, manufactured by Nihon Emulsion Co., Ltd.) were introduced into a 1,000 ml three-neck flask provided with a reflux device, were mixed together, and were thus subjected to dissolution. The inside atmosphere of the three-neck flask was then replaced by an N2 gas. The aqueous monomer solution having been prepared in the manner described above was then introduced into the three-neck flask. The resulting mixture was heated to a temperature of 65° C. to 70° C. in an oil bath, while the mixture was being stirred under the N2 gas atmosphere. At the stage at which the system had reached the temperature of 65° C. to 70° C., it was confirmed that the system had come into a semitransparent microemulsion state, and 2 g of ammonium persulfate was then added to the polymerization system. Polymerization was thus begun. The polymerization system was kept at the temperature of 65° C. to 70° C. with stirring, and a microgel was thus formed. After the polymerization had finished, acetone was added to the microgel suspension, and the microgel was thus precipitated. Subsequently, washing with acetone was performed three times, and the residual monomers and the surfactants were thus removed. The obtained precipitate was collected by filtration and dried under reduced pressure, and a white powder-like microgel dry product was thereby obtained. provided with a reflux device were mixed together were thus subjected to dissolution The aqueous monomer solution having been prepared in the manner above was then introduced into the three-neck flask The resulting mixture was heated to a temperature of 65° C. to 70° C. in an oil bath, while the mixture the temperature of 65° C. to 70° C., it was then added to the polymerization system Polymerization was kept at the temperature of 65° C. to 70° C. a microgel was thus formed the microgel was thus precipitated Subsequently, washing with acetone the residual monomers and the surfactants were thus removed The obtained precipitate was collected by filtration dried under reduced pressure a white powder-like microgel dry product was thereby obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A diclofenac submicron cream was prepared as follows: Oil phase--diclofenac diethylammonium 12.2 g, MCT oil 170 g, LIPOID E-80 30 g, α-tocopherol succinate 0.4 g; Aqueous phase--EDTA disodium salt 1 g, EMULFOR EL-620 25 g, glycerol 17.5 g, preservatives (methyl and propyl parabens) 0.5 g, reverse osmosis purified water to 1000 g. purified water to 1000 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In benzene were dissolved 4.0 g of 2-[(Z)-9-octadecen-1-yl)oxyethanol and 4.6 g of 2-bromoethyl phosphorodichloridate, and following dropwise addition of 1.5 g of pyridine under ice-cooling, the mixture was stirred at room temperature. The reaction mixture was treated by the procedure of Production Example 1 including hydrolysis, quaternization, purification by silica gel column chromatography and recrystallization from chloroform-acetone to give 0.52 g (9%) of the desired product. cooling

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 Grams of N,N-diethylaminoethyl methacrylate, 50 g. of methyl methacrylate, 1 g. of Dupanol ME, 1 g. of Emulphor ON-870, 6 g. of ethylene diacrylate, 1 g. of potassium persulfate, and 0.5 g. of sodium bisulfite are dissolved or mixed with 1,000 g. of water. This mixture is tumbled in a water bath at 60° C. for 24 hr. to obtain a crosslinked copolymer of methyl methacrylate and N,N-diethylaminoethyl acrylate. The crosslinked polymer is separated from the aqueous dispersion by the method described in Example 4. mixed with 1,000 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A diclofenac submicron cream was prepared as follows: Oil phase--diclofenac diethylammonium 12.2 g, MCT oil 170 g, LIPOID E-80 30 g, α-tocopherol succinate 0.4 g; Aqueous phase--EDTA disodium salt 1 g, EMULFOR EL-620 25 g, glycerol 17.5 g, preservatives (methyl and propyl parabens) 0.5 g, reverse osmosis purified water to 1000 g. purified water to 1000 g