JPH0390029A - Danazol suppository - Google Patents
Danazol suppositoryInfo
- Publication number
- JPH0390029A JPH0390029A JP1224378A JP22437889A JPH0390029A JP H0390029 A JPH0390029 A JP H0390029A JP 1224378 A JP1224378 A JP 1224378A JP 22437889 A JP22437889 A JP 22437889A JP H0390029 A JPH0390029 A JP H0390029A
- Authority
- JP
- Japan
- Prior art keywords
- polyoxyethylene
- danazol
- ether
- suppository
- alkyl ether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 title claims abstract description 32
- 229960000766 danazol Drugs 0.000 title claims abstract description 32
- 239000000829 suppository Substances 0.000 title claims abstract 9
- -1 polyoxyethylene Polymers 0.000 claims abstract description 37
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 20
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 238000000465 moulding Methods 0.000 claims abstract description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000005215 alkyl ethers Chemical class 0.000 claims abstract description 9
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 claims abstract description 8
- 229940116364 hard fat Drugs 0.000 claims abstract description 7
- QHZLMUACJMDIAE-UHFFFAOYSA-N 1-monopalmitoylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 claims abstract description 4
- 244000299461 Theobroma cacao Species 0.000 claims abstract description 3
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 claims abstract description 3
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 claims abstract description 3
- 235000001046 cacaotero Nutrition 0.000 claims abstract description 3
- 150000004667 medium chain fatty acids Chemical class 0.000 claims abstract description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 3
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 claims abstract 2
- 235000011187 glycerol Nutrition 0.000 claims description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 claims description 3
- QHZLMUACJMDIAE-SFHVURJKSA-N 1-hexadecanoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)CO QHZLMUACJMDIAE-SFHVURJKSA-N 0.000 claims description 2
- 235000014121 butter Nutrition 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- 235000019197 fats Nutrition 0.000 claims 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 abstract description 10
- 210000004877 mucosa Anatomy 0.000 abstract description 5
- 239000006216 vaginal suppository Substances 0.000 abstract description 3
- 201000009273 Endometriosis Diseases 0.000 abstract description 2
- 229940120293 vaginal suppository Drugs 0.000 abstract description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 abstract 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 abstract 1
- 239000004034 viscosity adjusting agent Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 19
- 238000010438 heat treatment Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 231100000017 mucous membrane irritation Toxicity 0.000 description 5
- 244000146493 Cryptotaenia japonica Species 0.000 description 4
- 235000004035 Cryptotaenia japonica Nutrition 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 210000004198 anterior pituitary gland Anatomy 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 210000001215 vagina Anatomy 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002357 endometrial effect Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 229920002675 Polyoxyl Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 239000003933 gonadotropin antagonist Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000019860 lauric fat Nutrition 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000008164 mustard oil Substances 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000037204 skin physiology Effects 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
童皇±曵七貝匁畳
本発明は、ダナゾール型剤に関し、更に詳しくは、ダナ
ゾールの粘膜吸収性及び安定性に優れたダナゾールの膣
坐剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a danazol-type preparation, and more particularly to a vaginal suppository of danazol that has excellent mucosal absorption and stability.
更泉曵盈酒
ダナゾールは、下垂体前葉でのゴナドトロピン分泌抑制
とそれに基づく卵巣でのエストロゲン産生低下を主な作
用機序とし、もっばら子宮内膜症治療の経口剤として市
販されている薬物であり、特開昭６１−１６１３＠公報
には、経口吸収の改善を図るダナゾール製剤が報告され
ている。Danazol is a drug whose main mechanism of action is to suppress gonadotropin secretion in the anterior pituitary gland and thereby reduce estrogen production in the ovaries, and is mainly marketed as an oral agent for the treatment of endometriosis. JP-A No. 61-1613@ has reported a danazol preparation that aims to improve oral absorption.
一方、ダナゾールの作用機序に関する最近の研究におい
て、腟内局所投与による子宮内膜組織への直接作用が提
案され、１９８８年８月１６日〜２６日に京都で開催さ
れた第８回国除肉分泌学会では、ダナゾール含有の腟内
リング製剤による治療効果が、また、１９８８年１０月
２３日〜２８日にブラジルで開催された第１２回世界産
婦人科学会では、ダナゾールの経膣カプセルによる治療
効果が夫々発表されている。On the other hand, in recent research on the mechanism of action of danazol, a direct effect on the endometrial tissue by local administration in the vagina was proposed, and the 8th National Demutilation Conference held in Kyoto from August 16th to 26th, 1988 Therapeutic effects of intravaginal ring preparations containing danazol were presented at the secretory conference, and the 12th World Congress of Obstetrics and Gynecology, held in Brazil from October 23 to 28, 1988, presented the treatment of danazol vaginal capsules. The effects have been announced.
Ｉが解゛しようとする
しかしながら、特開昭６１−１６１３＠公報には、腟内
局所投与製剤の言及はなく、その示唆すらもない。However, in JP-A-61-1613@, there is no mention or even suggestion of intravaginal topical preparations.
一方、ダナゾール含有の腟内リング製剤は、製剤の性質
上、腟内での正確な装着に熟練を要し、しかも使用後は
脱着を必要とし、患者が簡便に使用できる製剤とは言い
がたく、ダナゾールの経膣カプセルは、粘膜、特に膣粘
膜からの吸収性を高める技術はほとんど施されておらず
、薬物効率に問題がある。これらの難点を解決する製剤
として型剤、特に膣坐剤が想到されるが、一般に繁用さ
れる型剤基剤、例えば、カカオ脂、ハードファツト、サ
ポサイアー、ノバタ、ラウリン脂、グリセリルモノパル
ミテート、グリセリルモノステアレート、グリセロゼラ
チン又はポリエチレングリコール（平均分子１１０００
以上）を用いたダナゾール型剤では、上記経膣カプセル
と同様に粘膜吸収性が極めて不十分であることが、また
、上記型剤基剤に粘膜吸収性を高めるため、一般に繁用
されている可溶化剤、例えば、流動パラフィン、イソプ
ロピル主リステート、スクワラン、ポリオキシエチレン
硬化とマシ油、ポリオキシエチレンソルビタン脂肪酸エ
ステル又はデカグリセリン脂肪酸エステルを添加して調
製されたダナゾール型剤では、粘膜吸収性の改善は認め
られるものの、粘膜刺激性の発現又は温度安定性の低下
によるダナゾールの分解が本発明者らの厖大な実験によ
り確認された。On the other hand, intravaginal ring preparations containing danazol require skill to apply accurately in the vagina due to the nature of the preparation, and they also require removal after use, making it difficult to say that they are easy-to-use preparations for patients. , Danazol vaginal capsules have little technology to increase absorption through mucous membranes, especially vaginal mucous membranes, and there are problems with drug efficiency. Molded preparations, especially vaginal suppositories, have been considered as formulations that solve these difficulties, but commonly used molding agent bases such as cacao butter, hard fat, supporter, Novata, lauric fat, glyceryl monopalmitate, Glyceryl monostearate, glycerogelatin or polyethylene glycol (average molecular weight 11000
Danazol-type preparations using the above) have extremely insufficient mucosal absorption, similar to the above-mentioned vaginal capsules. Danazol-type preparations prepared with the addition of solubilizers, such as liquid paraffin, isopropyl-based lystate, squalane, hardened polyoxyethylene and mustard oil, polyoxyethylene sorbitan fatty acid esters or decaglycerin fatty acid esters, provide mucosally absorbable Although an improvement was observed, extensive experiments by the present inventors confirmed that danazol was decomposed due to the development of mucosal irritation or a decrease in temperature stability.
更に、ダナゾール型剤においては、粘膜吸収性を増大さ
せることにより、子宮内膜組織での直接作用に加え、下
垂体前葉での抗ゴナドトロピン作用による相乗効果が発
揮されることも本発明者らは解明した。Furthermore, the present inventors have also found that danazol-type drugs exert a synergistic effect through antigonadotrophin action on the anterior pituitary gland in addition to direct action on the endometrial tissue by increasing mucosal absorption. I figured it out.
１ を 決するための手段
本発明の目的は、粘膜、特に腟粘膜吸収性が良好で、か
つ粘膜刺激性が無く、しかも安定性に優れたダナゾール
型剤を提供することにある。An object of the present invention is to provide a danazol-type drug that has good absorbability into the mucous membranes, particularly the vaginal mucosa, is free from mucosal irritation, and has excellent stability.
本発明によれば、ダナゾールとポリオキシエチレンアル
キルエーテルとを含有してなる型剤が提供される。According to the present invention, a molding agent containing danazol and polyoxyethylene alkyl ether is provided.
本発明型剤において、ポリオキシエチレンアルキルエー
テルは、型剤基剤と可溶化剤の役割を兼備する。使用す
るポリオキシエチレンアルキルエーテルとしては、酸化
エチレンが１５モル以上付加したものであればよく、例
えば、ポリオキシエチレンラウリルエーテル、ポリオキ
シエチレンセチルエーテル、ポリオキシエチレンステア
リルエーテル、ポリオキシエチレンオレイルエーテル又
はポリオキシエチレンベヘニルエーテルが挙げられるが
、好ましくは、ポリオキシエチレンステアリルエーテル
又はポリオキシエチレンオレイルエーテルである。ポリ
オキシエチレンアルキルエーテルの使用量は、ダナゾー
ル１重量部に対して、０．１〜２０重量部、好ましくは
、０．２〜５重量部とする。In the molding agent of the present invention, polyoxyethylene alkyl ether serves both as a molding agent base and a solubilizer. The polyoxyethylene alkyl ether to be used may be one to which 15 moles or more of ethylene oxide is added, such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, or Examples include polyoxyethylene behenyl ether, preferably polyoxyethylene stearyl ether or polyoxyethylene oleyl ether. The amount of polyoxyethylene alkyl ether used is 0.1 to 20 parts by weight, preferably 0.2 to 5 parts by weight, per 1 part by weight of Danazol.
本発明型剤には、成型を高めるため、前記の一般に繁用
される型剤基剤を、または、稠度調整のため、グリセリ
ン、ポリエチレングリコール（平均分子量６００以下）
、プロピレングリコール又は中鎖脂肪酸トリグリセリド
等を必要に応じて添加してもよい。The molding agent of the present invention may contain the above-mentioned commonly used molding agent base to improve molding, or glycerin or polyethylene glycol (average molecular weight 600 or less) to adjust consistency.
, propylene glycol, medium chain fatty acid triglyceride, etc. may be added as necessary.
在里
本発明型剤の安定性、腟粘膜吸収性及び膣粘膜刺激性に
ついて以下に詳述する。試験に供した本発明型剤として
は、後述の実流例に記載した各製剤を、対照例としては
、以下に説明する四製剤を使用した。The stability, vaginal mucosal absorption, and vaginal mucosal irritation of the formulation of the present invention will be described in detail below. As the formulations of the present invention subjected to the test, each formulation described in the actual flow examples described below was used, and as control examples, the four formulations described below were used.
対照例１
ダナゾール３ｇ、ポリオキシエチレン硬化ヒマシ油（酸
化エチレン６０モル付加物）１９及びハードファツト（
ウイテプゾール５−５５．ミツバ貿易株式会社製）１ｇ
を加温下に練合し、ついでこれを型に注入し、冷却して
型剤１５個を製造した。Control example 1 3 g of danazol, polyoxyethylene hydrogenated castor oil (60 mol ethylene oxide adduct) 19 and hard fat (
Witepsol 5-55. (manufactured by Mitsuba Trading Co., Ltd.) 1g
The mixture was kneaded under heating, and then poured into molds and cooled to produce 15 molds.
対照例２
ダナゾール２ｇ、１ｃＪのポリソルベート８０及びハー
ドファツト（ウィテプゾール５−５５．ミツバ貿易株式
会社製＞１０９を加温下に練合し、ついでこれを型に注
入し、冷却して型剤１０個を製造した。Control Example 2 2 g of danazol, 1 cJ of polysorbate 80 and hard fat (Witepsol 5-55. manufactured by Mitsuba Boeki Co., Ltd. > 109) were kneaded under heating, then poured into a mold, cooled, and made into 10 mold agents. Manufactured.
対照例３
ダナゾール３ｇ及び２ｇのステアリン酸ポリオキシル４
０を加温下に練合し、ついでこれを型に注入し、冷却し
て型剤１５個を製造した。Control example 3 danazol 3g and 2g polyoxyl stearate 4
0 was kneaded under heating, and then poured into molds and cooled to produce 15 molds.
対照例４ ダナゾールの市販カプセル内容物。Control example 4 Commercially available capsule contents of Danazol.
（安定性）
被験製剤を６０℃で３０日間保存した後、各被験製剤中
の分解物の有無を薄層クロマトグラフ法により試験した
。(Stability) After storing the test preparations at 60° C. for 30 days, the presence or absence of decomposition products in each test preparation was tested by thin layer chromatography.
実施例１〜９の九型剤及び対照例４の製剤では、分解物
は皆無であった。これに対し、対照例１〜対照例３の三
型剤では分解物が認められた。In the Type 9 preparations of Examples 1 to 9 and the preparation of Control Example 4, there were no decomposition products. On the other hand, decomposition products were observed in the type 3 agents of Control Examples 1 to 3.
（膣粘膜吸収性）
７退会のウィスター系雌性ラット（１群２匹〉の腟内に
被験製剤を投与したのち、腟口をアロンアルファで接着
し、２．４．８及び２４時間後に層殺し、卵巣、子宮角
及び血漿中のダナゾール濃度を液体クロマトグラフ法に
より測定した。被験製剤としては、実施例１．３及び６
並びに対照例１及び４を選択した。各被験製剤の各ラッ
トに対するダナゾールの投与量は２００■／に９になる
ように設定した。結果を表に示す。(Absorbability of Vaginal Mucosa) After administering the test preparation into the vagina of 7 withdrawn Wistar female rats (2 rats per group), the vaginal opening was glued with Aron Alpha, and after 2.4.8 and 24 hours, the test preparation was stratified. Danazol concentrations in ovaries, uterine horns, and plasma were measured by liquid chromatography.The test preparations were Examples 1.3 and 6.
and Control Examples 1 and 4 were selected. The dose of danazol for each test formulation to each rat was set at 200 μ/9. The results are shown in the table.
（以下余白）
（膣粘膜刺激性）
家兎を用い膣粘膜刺激性の試験を行った。試験は、「新
しい皮膚の生理と安全性−接触化学物質の毒性評価」２
０８頁（１９８３年清至書院発行〉に記載された方法を
用いた。全実施例の型剤において、外観及び組織学上の
異常は全く認められなかった。これに対し、対照例１の
型剤では、異常が認められ膣粘膜刺激性があることが確
認された。(Left below) (Vaginal mucosal irritation) Vaginal mucosal irritation was tested using domestic rabbits. The test was “New Skin Physiology and Safety – Toxicity Evaluation of Contact Chemical Substances” 2
The method described in page 08 (published by Seishi Shoin, 1983) was used. No abnormality was observed in appearance or histology in the molds of all Examples. In contrast, the molds of Control Example 1 Abnormalities were observed with the drug, and it was confirmed that it was irritating to the vaginal mucosa.
叉盟狙ユ
ダナゾール３ｇ及びポリオキシエチレンオレイルエーテ
ル（酸化エチレン２０モル付加物）２９を加温下に練合
し、ついでこれを型に注入し、冷却して型剤１５個を製
造した。3 g of yudanazole and 29 g of polyoxyethylene oleyl ether (adduct of 20 moles of ethylene oxide) were kneaded under heating, and then poured into molds and cooled to produce 15 molds.
Ｘ簾里２
ダナゾール６ｇ、ポリオキシエチレンステアリルエーテ
ル（酸化エチレン２０モル付加物〉２．３ｇ及びグリセ
リン１．７ｇを加温下に練合し、ついでこれを型に注入
し、冷却して型剤３０個を製造した。X-Renri 2 6g of danazol, 2.3g of polyoxyethylene stearyl ether (20 mole adduct of ethylene oxide), and 1.7g of glycerin are kneaded under heating, then poured into a mold, cooled, and made into a molding agent. Thirty pieces were manufactured.
Ｘ旌盟旦
ダナゾール６９、ポリオキシエチレンオレイルエーテル
（酸化エチレン２０モル付加物）２．３９及びグリセリ
ン１．７ｇを加温下に練合し、ついでこれを型に注入し
、冷却して型剤３０個を製造した。Danazol 69, polyoxyethylene oleyl ether (20 mole adduct of ethylene oxide), and 1.7 g of glycerin are kneaded under heating, then poured into a mold, cooled, and molded. Thirty pieces were manufactured.
亙思班１
ダナゾール４ｇ、ポリオキシエチレンラウリルエーテル
＜ｉｌ化エチレン２１モル付加物）４ｇ及びグリセリン
２ｇを加温下線今後、これを型に注入し、冷却して型剤
２０個を製造した。亙子类1 4g of danazol, 4g of polyoxyethylene lauryl ether (adduct of 21 moles of ilized ethylene) and 2g of glycerin were heated and then poured into molds and cooled to produce 20 molds.
犬簾史互
ダナゾール４ｇ、ポリオキシエチレンセチルエーテル（
酸化エチレン３０モル付加物＞４ｇ及びグリセリン２ｇ
を加温下線今後、これを型に注入し、冷却して型剤２０
個をＷａ造した。4g of Inusen Shiga Danazol, polyoxyethylene cetyl ether (
30 mole adduct of ethylene oxide>4g and glycerin 2g
After heating the underline, pour it into the mold and cool it down to a molding agent of 20
I made a piece by Wa.
丈恵廻旦
ダナゾール３ｇ、ポリオキシエチレンステアリルエーテ
ル（Ｍ化エチレン２０モル付加物＞１及びハードファツ
ト（ウイテプゾール５−５５゜ミツバ貿易株式会社製）
１ｇを加温下に練合し、ついでこれを型に注入し、冷却
して型剤１５個を製造した。Takee Kaidan Danazol 3g, polyoxyethylene stearyl ether (M-ethylene 20 mole adduct>1 and hard fat (Witepsol 5-55° manufactured by Mitsuba Trading Co., Ltd.)
1 g was kneaded under heating, then poured into molds, and cooled to produce 15 molds.
大簾斑ユ
ダナゾール２ｇ、ポリオキシエチレンオレイルエーテル
（酸化エチレン２０モル付加物）１ｇ及びハードファツ
ト（ウィテプゾール５−５５．ミツバ貿易株式会社製＞
１０ｇを加温下線今後、これを型に注入し、冷却して型
剤１０個を製造した。2 g of large blind eudanazole, 1 g of polyoxyethylene oleyl ether (20 mole adduct of ethylene oxide) and hard fat (Witepsol 5-55. manufactured by Mitsuba Trading Co., Ltd.)
After heating, 10 g was poured into a mold and cooled to produce 10 molds.
太豊亘旦
ダナゾール２９及びポリオキシエチレンセチルエーテル
（酸化エチレン１５モル付加物〉０．２９を加温下に練
合し、これを型に注入し、冷却して型剤１０ｍを製造し
た。Taiho Watadan Danazol 29 and polyoxyethylene cetyl ether (15 mol ethylene oxide adduct) 0.29 were kneaded under heating, poured into a mold, and cooled to produce 10 m of mold agent.
犬簾狙旦
ダナゾール１９及びポリオキシエチレンオレイルエーテ
ル（酸化エチレン２０モル付加物＞２０９を加温下に練
合し、これを型に注入し、冷却して型剤５個を製造した
。Danazol 19 and polyoxyethylene oleyl ether (ethylene oxide 20 mole adduct >209) were kneaded under heating, poured into molds, and cooled to produce 5 molds.
及咀曵Ａ逮
本発明のダナゾール型剤は、温度安定性及び粘膜吸収性
に優れ、しかも粘膜刺激性が無い製剤であり、ダナゾー
ルの子宮内組織への直接作用と血中を介する下垂体前葉
での抗ゴナドトロピン作用の相乗効果が期待でき、ダナ
ゾールが本来持つ薬効を十二分に発揮させる製剤である
。The danazol-type preparation of the present invention is a preparation that has excellent temperature stability and mucosal absorption, and is non-irritating to the mucous membrane.Danazol acts directly on intrauterine tissue and on the anterior pituitary gland through the blood. A synergistic effect of the antigonadotropin action can be expected in danazol, and it is a formulation that fully demonstrates the original medicinal effects of danazol.
Claims (6)
ルを含有することを特徴とする坐剤。(1) A suppository containing danazol and polyoxyethylene alkyl ether.
アルキルエーテルが０．１〜２０重量部である請求項１
記載の坐剤。(2) Claim 1, wherein the amount of polyoxyethylene alkyl ether is 0.1 to 20 parts by weight per 1 part by weight of danazol.
Suppositories as described.
キシエチレンラウリルエーテル、ポリオキシエチレンセ
チルエーテル、ポリオキシエチレンステアリルエーテル
、ポリオキシエチレンオレイルエーテル又はポリオキシ
エチレンベヘニルエーテルである請求項１又は２記載の
坐剤。(3) The suppository according to claim 1 or 2, wherein the polyoxyethylene alkyl ether is polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether or polyoxyethylene behenyl ether. .
は３記載の坐剤。(4) The suppository according to claim 1, 2 or 3, containing a molding agent or a consistency regulator.
アー、ノバタ、ラウリン脂、グリセリルモノパルミテー
ト、グリセリルモノステアレート、グリセロゼラチン又
はポリエチレングリコール（平均分子量１０００以上）
である請求項４記載の坐剤。(5) The molding agent is cacao butter, hardfat, saposire, Novata, laurin fat, glyceryl monopalmitate, glyceryl monostearate, glycerogelatin or polyethylene glycol (average molecular weight 1000 or more)
The suppository according to claim 4.
ール（平均分子量６００以下）、プロピレングリコール
又は中鎖脂肪酸トリグリセリドである請求項４記載の坐
剤。(6) The suppository according to claim 4, wherein the consistency regulator is glycerin, polyethylene glycol (average molecular weight 600 or less), propylene glycol, or medium chain fatty acid triglyceride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1224378A JP2927830B2 (en) | 1989-09-01 | 1989-09-01 | Danazol suppository |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1224378A JP2927830B2 (en) | 1989-09-01 | 1989-09-01 | Danazol suppository |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0390029A true JPH0390029A (en) | 1991-04-16 |
| JP2927830B2 JP2927830B2 (en) | 1999-07-28 |
Family
ID=16812818
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1224378A Expired - Fee Related JP2927830B2 (en) | 1989-09-01 | 1989-09-01 | Danazol suppository |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2927830B2 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0676146A1 (en) * | 1994-03-11 | 1995-10-11 | Fuji Oil Company, Limited | Anti-blooming composition, and laurin fat and chocolate containing the same |
| JP2001511773A (en) * | 1997-01-24 | 2001-08-14 | フェムファーマ | Pharmaceutical preparations and methods for their regional administration |
| JP2004323454A (en) * | 2003-04-25 | 2004-11-18 | Chisso Corp | Medicinal agent |
| EP1611878A1 (en) * | 1997-01-24 | 2006-01-04 | FemmePharma Holding Company, Inc. | Pharmaceutical preparations and methods for their regional administration |
| US8226972B2 (en) | 2001-12-20 | 2012-07-24 | Femmepharma Holding Company, Inc. | Vaginal delivery of drugs |
| US9173836B2 (en) | 2003-01-02 | 2015-11-03 | FemmeParma Holding Company, Inc. | Pharmaceutical preparations for treatments of diseases and disorders of the breast |
| JP2018519345A (en) * | 2015-07-08 | 2018-07-19 | ドクトル ファルク ファルマ ゲーエムベーハー | Pharmaceutical preparations for the treatment of inflammatory changes of the rectum |
-
1989
- 1989-09-01 JP JP1224378A patent/JP2927830B2/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0676146A1 (en) * | 1994-03-11 | 1995-10-11 | Fuji Oil Company, Limited | Anti-blooming composition, and laurin fat and chocolate containing the same |
| JP2001511773A (en) * | 1997-01-24 | 2001-08-14 | フェムファーマ | Pharmaceutical preparations and methods for their regional administration |
| EP1611878A1 (en) * | 1997-01-24 | 2006-01-04 | FemmePharma Holding Company, Inc. | Pharmaceutical preparations and methods for their regional administration |
| JP2010138196A (en) * | 1997-01-24 | 2010-06-24 | Femmepharma Holding Co Inc | Pharmaceutical preparations and methods for their regional administration |
| EP2316424A1 (en) * | 1997-01-24 | 2011-05-04 | FemmePharma Holding Company, Inc. | Pharmaceutical preparations and methods for their regional administration |
| US8226972B2 (en) | 2001-12-20 | 2012-07-24 | Femmepharma Holding Company, Inc. | Vaginal delivery of drugs |
| US9173836B2 (en) | 2003-01-02 | 2015-11-03 | FemmeParma Holding Company, Inc. | Pharmaceutical preparations for treatments of diseases and disorders of the breast |
| JP2004323454A (en) * | 2003-04-25 | 2004-11-18 | Chisso Corp | Medicinal agent |
| JP2018519345A (en) * | 2015-07-08 | 2018-07-19 | ドクトル ファルク ファルマ ゲーエムベーハー | Pharmaceutical preparations for the treatment of inflammatory changes of the rectum |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2927830B2 (en) | 1999-07-28 |
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