Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Wearing apparel – fabric – or cloth
Reexamination Certificate
2001-01-10
2002-08-13
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Wearing apparel, fabric, or cloth
C424S401000, C424S405000, C424S443000, C424S449000, C424S484000, C424S486000
Reexamination Certificate
active
06432431
ABSTRACT:
TECHNICAL FIELD
The present invention relates to steroid-containing gel patches (cataplasms) and a process for producing the same; more specifically, the present invention relates to steroid-containing gel patches comprising crotamiton as a stabilizer and a surfactant and being stable over time, and a process for producing the same.
BACKGROUND ART
Adrenal cortex hormones (steroids) and the like have conventionally been used as principal drugs for allergic dermal diseases such as eczema, the dermatitis group, psoriasis, prurigo, erythema, insect bite, chronic discoid lupus erythematosus, asialoid lichen, lichen ruber planus, and atopic dermatitis. Sticking dosage forms described in Japanese Patent Laid-open Nos. 51330/1988 and 53354/1996 have been known to contain such steroids as effective ingredients.
The sticking dosage form described in Japanese Patent Laid-open No. 51330/1988 is prepared by blending steroids in an adhesive gel base containing a water-soluble polymer, water and a water-retentive agent as essential ingredients. So as to increase the solubility and dispersibility of steroids in water, described in Japanese Patent Laid-Open No. 51330/1988 is blending of oil components such as crotamiton, benzyl alcohol, isopropyl myristate, ethylene glycol, diethyl sebacate, and 2-ethyl-5-pyrrolidone as well as surfactants. The sticking dosage form described in Japanese Patent Laid-open No. 53354/1996, of which the inventors are partially overlapped with those of the present invention and the assignee is the same as the assignee of the present invention, is prepared by blending adrenal cortex hormones in base components comprising a water-soluble polymer, a moisturizer, water, a dissolution agent and/or an absorption promoting agent; and the dissolution agent or absorption promoting agent includes oleic acid, glycol salicylate, benzyl alcohol, isopropylmyristate, crotamiton, oleyl alcohol, mint oil, eucalyptus oil, limonene, isopulegol, 3-1-menthoxypropan-1,2-diol, or other essential oils or surfactants.
DISCLOSURE OF THE INVENTION
When such conventional sticking dosage forms are applied to so-called gel patches with a relatively high water content in the bases, however, steroids at their dissolution state are rapidly hydrolyzed; and additionally, the adhesive strength of the resulting gel patch is decreased over time, disadvantageously. Therefore, such conventional sticking dosage forms are not yet satisfactory from the respect of the stability of the dosage forms over time.
The present invention has been achieved in terms of the problems of the conventional techniques. It is a purpose of the present invention to provide gel patches with a remarkably excellent stability over time, where the decomposition of steroids can be sufficiently prevented despite of dissolution states of the steroids. In the gel patches described above, the adhesive strength is stable over time and neither so-called bleeding due to phase separation in the base nor so-called stickiness due to the decrease of the adhesive force of the base occurs. It is also an object of the present invention to provide a process for efficiently producing the above mentioned gel patches.
The present inventors have made investigations so as to attain the purpose. Consequently, the inventors have found that a gel patch containing steroids as effective ingredients can comply with- the purpose even at dissolution state, when the gel patch is blended with a considerably larger volume of crotamiton as being a stabilizer compared to that employed in conventional sticking dosage forms, and with a surfactant having its predetermined blend ratio to crotamiton. Thus, the present invention has been achieved.
The gel patch (cataplasm) of the present invention is a steroid-containing gel patch containing a steroid at 0.005 to 0.05% by weight (abbreviated as wt % hereinbelow), crotamiton below 15 wt % as a stabilizer and a surfactant, as the effective ingredients in the base, wherein the amount of the crotamiton blended is 200- to 3000-fold the weight of the steroid blended and the amount of the surfactant blended is {fraction (1/20)}- to ⅕-fold the weight of the crotamiton blended.
The process for producing the gel patch in accordance with the present invention comprises a step of mixing 0.005 to 0.05 part by weight of the steroid with crotamiton at an amount 200- to 3000-fold the weight of the steroid and at 15 parts by weight or less, to recover a solution of the steroid in crotamiton, a step of mixing together a surfactant at an amount {fraction (1/20)}- to ⅕-fold the weight of crotamiton, water, a water-soluble polymer, and a moisturizer to recover a homogeneous kneaded mixture, and a step of adding the solution of the steroid in crotamiton to the kneaded mixture to recover a gel patch in which the steroid is homogeneously dispersed at dissolution state.
BEST MODE FOR CARRYING OUT THE INVENTION
The steroid-containing gel patch of the present invention is now described in detail hereinbelow. The steroid contained as the effective ingredient in the gel patch of the present invention includes for example diflucortolone valerate, difluprednate, prednisolone acetate valerate, betametasone valerate, dexametasone valerate, beclometasone propionate, hydrocortisone propionate butyrate, diflorazone acetate, dexametasone propionate, betametasone dipropionate, fluocinolone acetonide, triamcinolone acetonide, dexametasone, methylprednisolone, prednisolone, hydrocortisone, parametasone, betametasone, sodium betametasone phosphate, dexametasone acetate, cortisone acetate, hydrocortisone acetate,fluocinonide,fluorometholone,methylprednisolone acetate, halcinonide, budesonide, and alclometasone propionate; among them, a preference is given to betametasone valerate, dexametasone valerate, prednisolone acetate valerate, beclometasone propionate and fluocinolone acetonide. Betametasone valerate is particularly preferable for gel patches intended for eczema, dermatitis and atopic dermatitis and the like.
The steroids described above are contained at 0.005 wt % to 0.05 wt %, preferably at 0.01 wt % to 0.04 wt %, more preferably at 0.01 wt % to 0.03 wt % in gel patch bases. When the steroid content is less than 0.005 wt %, sufficient pharmacological effects can be yielded with much difficulty; when the steroid content is more than 0.05 wt %, alternatively, the amount of the steroid blended in the gel patch is so excessive that the imbalance between crotamiton and the surfactant then occurs, resulting in no procured steroid stability and no stability of the dosage form.
As effective ingredients, contained in the gel patches of the present invention are crotamiton as a stabilizer and a surfactant in their predetermined amounts. As described below, the use of crotamiton at a predetermined blend ratio to steroids and a surfactant at a predetermined blend ratio to the crotamiton in combination brings about the advantages of the present invention as described below, such as sufficient stability of steroids at dissolution state over time. Alternatively, dissolution agents except for crotamiton, such as fatty acid esters including diethyl sebacate and isopropyl myristate, can never sufficiently dissolve steroids, while polyethylene glycol and benzyl alcohol and the like eventually cause inconveniences such as an occurrence of steroid crystallization in the gel patch base. Thus, such dissolution agents can never attain the stability of steroids at dissolution state over time.
It is required that the amount of crotamiton blended in the gel patch of the present invention is below 15 wt % in the base (gel patch base or cataplasm base) and is 200- to 3000-fold the weight of the steroid blended therein. Preferably, the amount of crotamiton blended in the gel patch of the present invention is below 13 wt % in the base and is 250-to 1500-fold the weight of the steroid blended therein. More preferably, the amount of crotamiton blended in the gel patch of the present invention is below 10 wt % in the base and is 300-to 1200-fold the weight of the steroid b
Muta Kazunori
Tsuru Seiichiro
Yamahata Taro
Fitch Even Tabin & Flannery
Hisamitsu Pharmaceutical Co. Inc.
Sheikh Humera N.
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