JPH0359917B2 - - Google Patents
Info
- Publication number
- JPH0359917B2 JPH0359917B2 JP17648583A JP17648583A JPH0359917B2 JP H0359917 B2 JPH0359917 B2 JP H0359917B2 JP 17648583 A JP17648583 A JP 17648583A JP 17648583 A JP17648583 A JP 17648583A JP H0359917 B2 JPH0359917 B2 JP H0359917B2
- Authority
- JP
- Japan
- Prior art keywords
- acetonide
- fluocinolone
- compound
- present
- butyrate
- 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.)
- Expired
Links
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 claims description 18
- 229940043075 fluocinolone Drugs 0.000 claims description 7
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 20
- 230000000694 effects Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- SNHRLVCMMWUAJD-SUYDQAKGSA-N betamethasone valerate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O SNHRLVCMMWUAJD-SUYDQAKGSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000003246 corticosteroid Substances 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 3
- -1 compound betamethasone 17-valerate Chemical class 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 230000005923 long-lasting effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000002688 persistence Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 206010033546 Pallor Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 241000287227 Fringillidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960004311 betamethasone valerate Drugs 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、抗炎症作用を有する新規なコルチコ
ステロイド化合物、すなわちフルオシノロン16，
17−アセトニド21−酪酸エステル（11β，16α，
17α，21−テトラヒドロキシ−6α，9α−ジフルオ
ロ−プレグナ−１，４−ジエン−３，20−ジオン
16，17−アセトニド21−ブチレート）およびその
製造法に関するものである。
最近、数多くの抗炎症作用を有するコルチコス
テロイドが、内用又は外用の医薬品として臨床に
用いられている。特に皮フ科領域では、各種の疾
患に、各種のコルチコステロイドがクリーム・軟
膏・ローシヨンなどの剤形として、用いられてい
る。しかしながら、これらの薬物には、それぞれ
欠点があり、かならずしも満足すべき薬剤とは云
えない。本発明者らは、この点を考慮し、より有
用な化合物を開発すべく研究した結果、本発明に
より次式（）で表わされるフルオシノロン16，
17−アセトニド21−酪酸エステルを提供すること
に成功した。
すなわち、本発明に係る化合物（）は、上記
の薬理作用において著しく速効性を有し、しかも
適当な持続性をもかねそなえている有用な物質で
ある。
従来、臨床薬として使用されているベータメタ
ゾン17−バレレート（吉草酸ベータメタゾン）と
フルオシノロン16，17−アセトニドは、前者が比
較的速効性であるのに比し、後者は遅効性であ
る。特に、後者は遅効性である上に作用が持続す
るので、外用といえでも大量使用あるいは繰り返
えし使用により、コルチコステロイドの副作用と
しての全身作用が現われてくるきらいがある。こ
の点について、数多くの結果が臨床医により報告
されているが、効力が持続するという点におい
て、やはり特徴を有するので使用されている現状
にある。本発明者らはこの両者の欠点を除き、し
かもそれらの利点をあわせ有する薬物を発見する
ため、各種の21−エステルを製造し、その作用を
検討したところ、ベータメタゾン17−バレレート
の21−エステル類は、ベータメタゾン17−バレレ
ートよりもさらに吸収が早く、すぐ効力が失われ
てしまうという傾向にあるらしいこと、そして、
結果的に血管収縮作用が低く、目的の薬物として
不適当であることがわかつた（例えば、効力試験
の対照化合物ベータメタゾン17−バレレート21−
ブチレートなど）。一方、フルオシノロン16，17
−アセトニドの21−エステル類は、かなり有効で
あり、その幾つかは速効性且つ持続性であること
がわかつた。しかし、多くは持続性という点でや
やフルオシノロン16，17−アセトニドに劣る。し
かるに、本発明に係る化合物（）は、その中で
も持続性に優れており、フルオシノロン16，17−
アセトニドよりその値が高い傾向にあることがわ
かつた。本発明に係る化合物（）が、いかに優
れた速効性と持続性を有しているかは、後述の試
験例（パツチテスト）によつて明らかである。
本発明に係る化合物（）は、フルオシノロン
16，17−アセトニドのエステル化反応により容易
に製造することができる。エステル化の方法とし
ては、エステル化の常法により、ピリジンのよう
な第三級アミンの存在下、無水酪酸または酪酸ハ
ライドを用いる。酪酸ハライドを用いる場合は、
低温、短時間で反応が終了し、無水酪酸を用いる
場合は、室温、数時間で反応が完結する。具体的
方法は、種々の条件により適宜任意の方法を用い
ることができる。反応終了后、目的とする化合物
は、通常の操作方法により単離され、再結晶等に
より精製することができる。
本発明に係る化合物（）は、安定な結晶体と
して得られ、外用剤として目的に応じて軟膏・ク
リーム・ローシヨンなどの剤形に調製され、臨床
に提供することができる。
以下に、本発明に係る化合物（）の有効性を
証明するものとして、ヒトの皮膚による血管収縮
作用を検討した結果（Mckenzie−Stoughton法）
を参考的に記載する。
効力試験
本発明に係る化合物（）ならびに対照試験化
合物３種をそれぞれ、白色ワセリンをベース（基
剤）とした0.1％と0.01％濃度（ｗ／ｗ）の軟膏
に調製した。これらの試験用軟膏を、無作為に割
り付け、パツチテスト用絆創膏〔フインチヤンバ
ー：エピテスト社製造（フインランド）〕とし、
判定に関与しない第三者により一定量（約20mg）
を塗布したものを、健常な成人男子10名の両前腕
屈側部に貼り付け、16時間後に絆創膏を除去す
る。皮膚に残存する薬剤をぬぐい去り、石ケンに
て軽く洗い流したのち、２時間後および24時間後
の蒼白度を２名の判定者によつて判定した。判定
は、蒼白度を顕著（＋＋＋）、中等程度（＋＋）、
軽度（＋）および無効（−）の４段階に分け、そ
れぞれ３点、２点、１点および０点の得点を与
え、被験者10名の結果を集計し、２名の判定者の
平均値として算出した。
なお、本効力試験において比較のために用いた
対照化合物としては、本発明に係る化合物（）
の基本体であるフルオシノロン16，17−アセトニ
ドおよび臨床上有用なそしてスクリーニングの基
準薬ベータメタゾン17−バレレートに新たに合成
したこのベータメタゾン17−バレレートの21−ブ
チレートの３種を使用した。
効力試験結果から明らかなように、本発明に係
る化合物（）は、判定２時間後も24時間後もい
ずれもすべての対照薬より強い活性を示し、有用
さが証明された。すなわち、0.1％の場合、本発
明化合物（）は、フルオシノロン16，17−アセ
トニドよりも速効性があり、持続性は同等であつ
た。また、0.01％では、、速効性が優れている上
に、24時間後の値がフルオシノロン16，17−アセ
トニドのそれよりも大きく、持続性においても優
れていることがわたつた。この結果から、本発明
の化合物（）は、ベータメタゾン17−バレレー
トよりも速効性に優れ、フルオシノロン16，17−
アセトニドと同等もしくはそれ以上の持続性を有
すると云える。0.01％以下の濃度でも有効である
ことが予測され、臨床上僅かな使用量ですみ、従
つて副作用（全身作用）の点からも有益な薬物で
あると云える。
The present invention describes novel corticosteroid compounds with anti-inflammatory effects, namely fluocinolone 16,
17-acetonide 21-butyric acid ester (11β, 16α,
17α,21-tetrahydroxy-6α,9α-difluoro-pregna-1,4-diene-3,20-dione
16,17-acetonide 21-butyrate) and its production method. Recently, a number of corticosteroids with anti-inflammatory effects have been used clinically as internal or external medicines. Particularly in the field of dermatology, various corticosteroids are used in the form of creams, ointments, lotions, etc. for various diseases. However, each of these drugs has its own drawbacks and cannot necessarily be said to be a satisfactory drug. The present inventors took this point into consideration and as a result of research to develop a more useful compound, the present inventors developed fluocinolone 16, which is represented by the following formula ().
17-acetonide 21-butyric acid ester was successfully provided. That is, the compound (2) according to the present invention is a useful substance that has extremely fast-acting effects in the above-mentioned pharmacological actions and also has an appropriate sustainability. Betamethasone 17-valerate (betamethasone valerate) and fluocinolone 16,17-acetonide, which have been conventionally used as clinical drugs, are relatively fast-acting, while the latter is slow-acting. In particular, the latter is slow-acting and has a long-lasting effect, so even if it is used externally, systemic effects as a side effect of corticosteroids are likely to occur when used in large quantities or repeatedly. In this regard, a large number of results have been reported by clinicians, but it is still used because it has the characteristic of long-lasting efficacy. The present inventors produced various 21-esters and investigated their effects in order to eliminate both of these drawbacks and discover a drug that also has the advantages. It seems that it is absorbed even more quickly than betamethasone 17-valerate and tends to lose its potency quickly, and
As a result, it was found that the vasoconstrictor effect was low and that it was inappropriate as a target drug (for example, the control compound betamethasone 17-valerate 21-
butyrate, etc.). On the other hand, fluocinolone 16, 17
-21-esters of acetonide have been found to be quite effective, some of them fast-acting and long-lasting. However, most are slightly inferior to fluocinolone 16,17-acetonide in terms of persistence. However, the compound () according to the present invention has excellent persistence among them, and is superior to fluocinolone 16,17-
It was found that the value tends to be higher than that of acetonide. It is clear from the test example (patch test) described below how the compound () according to the present invention has excellent immediate effect and sustainability. The compound () according to the present invention is fluocinolone
It can be easily produced by esterification reaction of 16,17-acetonide. As for the esterification method, butyric anhydride or butyric acid halide is used in the presence of a tertiary amine such as pyridine according to a conventional esterification method. When using butyric acid halide,
The reaction is completed in a short time at low temperature, and when butyric anhydride is used, the reaction is completed in several hours at room temperature. As a specific method, any suitable method can be used depending on various conditions. After the reaction is completed, the target compound can be isolated by a conventional method and purified by recrystallization or the like. The compound () according to the present invention is obtained as a stable crystalline substance, and can be prepared as an external preparation into a dosage form such as an ointment, cream, or lotion depending on the purpose, and can be provided clinically. The following is the result of examining the vasoconstriction effect of human skin (Mckenzie-Stoughton method) as proof of the effectiveness of the compound () according to the present invention.
are listed for reference. Efficacy Test The compound according to the present invention () and three control test compounds were prepared into ointments with a white petrolatum base of 0.1% and 0.01% (w/w), respectively. These test ointments were randomly assigned to be used as a patch test bandage [Finch Yambar: manufactured by Epitest (Finland)].
A fixed amount (approximately 20 mg) is administered by a third party not involved in the determination.
The plaster was applied to the flexors of both forearms of 10 healthy male adults, and the bandage was removed 16 hours later. After wiping off the drug remaining on the skin and gently rinsing with soap, two judges judged the degree of pallor 2 and 24 hours later. The pallor is marked (+++), moderate (++),
Divided into four levels: mild (+) and ineffective (-), scores of 3 points, 2 points, 1 point, and 0 points were given respectively.The results of 10 subjects were aggregated, and the average value of the two judges was calculated. Calculated. In addition, as a control compound used for comparison in this efficacy test, the compound according to the present invention ()
Fluocinolone 16,17-acetonide, which is the basis of betamethasone 17-valerate, which is a clinically useful and standard drug for screening, and the newly synthesized 21-butyrate of betamethasone 17-valerate were used. As is clear from the efficacy test results, the compound () according to the present invention showed stronger activity than all the control drugs both 2 hours and 24 hours after the determination, proving its usefulness. That is, at 0.1%, the compound of the present invention () had a faster effect than fluocinolone 16,17-acetonide, and the duration was equivalent. In addition, at 0.01%, not only the immediate effect was excellent, but the value after 24 hours was greater than that of fluocinolone 16,17-acetonide, indicating that it was excellent in persistence. From these results, the compound of the present invention () has superior rapid-acting properties to betamethasone 17-valerate, and fluocinolone 16,17-valerate.
It can be said that it has a durability equivalent to or longer than that of acetonide. It is predicted to be effective even at a concentration of 0.01% or less, requiring only a small amount to be used clinically, and therefore can be said to be a beneficial drug in terms of side effects (systemic effects).
【表】
次に、本発明に係る化合物の製造の実施例を掲
げ説明する。
実施例 １
フルオシノロン16，17−アセトニド100mgをピ
リジン４mlに溶解し、これに無水酪酸0.2mlを加
え、室温にて４時間反応させた。次いで、反応液
を氷水中へ注入し、クロロホルムを用いて抽出し
た。クロロホルム抽出層を、希塩酸、希重炭酸ソ
ーダ液で洗浄し、最后に水で充分洗い、芒硝にて
乾燥し、減圧下に溶媒を留去して、結晶性粗生成
物110mgを得た。これをアセトン−ｎ−ヘキサン
にて再結晶すると、融点272−274℃のフルオシノ
ロン16，17−アセトニド21−ブチレート97mgが得
られた。
このものは、次に示すようなスペクトル・デー
タと元素分析値を有する。
NMR（CDCl3）δ：0.87（3H，ｓ，C18−CH3）、
0.90〜1.12（3H，ｍ，−CH2CH2CＨ 3）、1.14
（3H，ｓ，C19−CH3）、1.40と1.54（各3H，
ｓ，[Table] Next, examples of the production of compounds according to the present invention will be described. Example 1 100 mg of fluocinolone 16,17-acetonide was dissolved in 4 ml of pyridine, 0.2 ml of butyric anhydride was added thereto, and the mixture was reacted at room temperature for 4 hours. Then, the reaction solution was poured into ice water and extracted using chloroform. The chloroform extract layer was washed with dilute hydrochloric acid and dilute sodium bicarbonate solution, and finally thoroughly washed with water, dried over Glauber's salt, and the solvent was distilled off under reduced pressure to obtain 110 mg of a crystalline crude product. This was recrystallized from acetone-n-hexane to obtain 97 mg of fluocinolone 16,17-acetonide 21-butyrate having a melting point of 272-274°C. This item has the following spectral data and elemental analysis values. NMR ( CDCl3 ) δ: 0.87 (3H, s, C18 - CH3 ),
0.90-1.12 (3H, m , -CH2CH2CH3 ) , 1.14
(3H, s, C 19 −CH 3 ), 1.40 and 1.54 (3H,
s,
【式】）、5.05（2H，ｓ，
C21−CH2）、5.12（1H，ｂ，C11−OH）、6.39
（1H，dd，Ｊ＝６Hzと２Hz，C2−Ｈ）、6.48
（1H，ｓ，C4−Ｈ）、7.35（1H，ｄ，Ｊ＝６
Hz，C1−Ｈ）．
IRνKBr naxcm-1：3420，1740，1718，1665，1615，
1605，1380，1280，1250，1220，1170，
1060，900，858，700.
MS：ｍ／ｅ 522（M+）．
元素分析値 （C28H36F2O7として）：
理論値：Ｃ，64.35；Ｈ，6.94.
実験値：Ｃ，64.77；Ｈ，6.86.
実施例 ２
フルオシノロン16，17−アセトニド100mgをピ
リジン６mlに溶解し、０℃に冷却した。これに、
酪酸クロリド0.3mlを含むクロロホルム４mlの溶
液を加え、10分間軽く撹拌した。次いで、反応液
を氷水にあけ、以下、実施例１と同様に処理する
と、融点272−274℃のフルオシノロン16，17−ア
セトニド21−ブチレート97.5mgが得られた。この
化合物は、上記実施例１で得られたものと混融し
て融点降下を示さず、スペクトルも一致した。[Formula]), 5.05 (2H, s, C 21 −CH 2 ), 5.12 (1H, b, C 11 −OH), 6.39
(1H, dd, J = 6Hz and 2Hz, C 2 −H), 6.48
(1H, s, C 4 −H), 7.35 (1H, d, J=6
Hz, C 1 −H). IRν KBr nax cm -1 : 3420, 1740, 1718, 1665, 1615,
1605, 1380, 1280, 1250, 1220, 1170,
1060, 900, 858, 700. MS: m/e 522 (M + ). Elemental analysis value (as C 28 H 36 F 2 O 7 ): Theoretical value: C, 64.35; H, 6.94. Experimental value: C, 64.77; H, 6.86. Example 2 Fluocinolone 16,17-acetonide 100 mg in pyridine 6 ml and cooled to 0°C. to this,
A solution of 4 ml of chloroform containing 0.3 ml of butyric acid chloride was added, and the mixture was gently stirred for 10 minutes. Next, the reaction solution was poured into ice water and treated in the same manner as in Example 1 to obtain 97.5 mg of fluocinolone 16,17-acetonide 21-butyrate having a melting point of 272-274°C. This compound was mixed with the compound obtained in Example 1, showed no drop in melting point, and had a spectrum that matched that of the compound obtained in Example 1 above.
Claims (1)
21−ブチレート化合物。 ２ フルオシノロン16，17−アセトニドを第三級
アミンの存在下に無水酪酸あるいは酪酸クロリド
と反応させることを特徴とするフルオシノロン
16，17−アセトニド21−ブチレートの製造法。[Claims] 1. General formula Fluocinolone 16,17-acetonide-
21-Butyrate compounds. 2 Fluocinolone characterized by reacting fluocinolone 16,17-acetonide with butyric anhydride or butyric acid chloride in the presence of a tertiary amine
Method for producing 16,17-acetonide 21-butyrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17648583A JPS6067496A (en) | 1983-09-26 | 1983-09-26 | Fluocinolone 16,17-acetonide 21-butylate and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17648583A JPS6067496A (en) | 1983-09-26 | 1983-09-26 | Fluocinolone 16,17-acetonide 21-butylate and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6067496A JPS6067496A (en) | 1985-04-17 |
| JPH0359917B2 true JPH0359917B2 (en) | 1991-09-12 |
Family
ID=16014483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17648583A Granted JPS6067496A (en) | 1983-09-26 | 1983-09-26 | Fluocinolone 16,17-acetonide 21-butylate and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6067496A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9100342D0 (en) * | 1991-02-04 | 1991-02-04 | Astra Ab | NOVEL STEROID ESTERS |
-
1983
- 1983-09-26 JP JP17648583A patent/JPS6067496A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6067496A (en) | 1985-04-17 |
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