JPH11315035A - Ointment preparation - Google Patents
Ointment preparationInfo
- Publication number
- JPH11315035A JPH11315035A JP11049756A JP4975699A JPH11315035A JP H11315035 A JPH11315035 A JP H11315035A JP 11049756 A JP11049756 A JP 11049756A JP 4975699 A JP4975699 A JP 4975699A JP H11315035 A JPH11315035 A JP H11315035A
- Authority
- JP
- Japan
- Prior art keywords
- ointment
- average molecular
- polyethylene glycol
- ointment preparation
- weight
- 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
- 239000002674 ointment Substances 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 21
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical class C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims abstract description 17
- 239000002202 Polyethylene glycol Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract description 9
- 229910052708 sodium Inorganic materials 0.000 abstract description 9
- 239000011734 sodium Substances 0.000 abstract description 9
- 229910019142 PO4 Inorganic materials 0.000 abstract description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract description 7
- 239000010452 phosphate Substances 0.000 abstract description 7
- CJGYSWNGNKCJSB-YVLZZHOMSA-N bucladesine Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](OC(=O)CCC)[C@@H]2N1C(N=CN=C2NC(=O)CCC)=C2N=C1 CJGYSWNGNKCJSB-YVLZZHOMSA-N 0.000 abstract 1
- 229960005263 bucladesine Drugs 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 150000002334 glycols Chemical class 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 11
- 239000000203 mixture Substances 0.000 description 8
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 7
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 6
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229920000592 inorganic polymer Polymers 0.000 description 4
- 230000001953 sensory effect Effects 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 229940095074 cyclic amp Drugs 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- -1 inorganic acid salt Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- FJNCXZZQNBKEJT-UHFFFAOYSA-N 8beta-hydroxymarrubiin Natural products O1C(=O)C2(C)CCCC3(C)C2C1CC(C)(O)C3(O)CCC=1C=COC=1 FJNCXZZQNBKEJT-UHFFFAOYSA-N 0.000 description 1
- 206010011985 Decubitus ulcer Diseases 0.000 description 1
- NVGDLMUKSMHEQT-FRJWGUMJSA-N N(6)-butyryl-cAMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2NC(=O)CCC)=C2N=C1 NVGDLMUKSMHEQT-FRJWGUMJSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- MKPXGEVFQSIKGE-UHFFFAOYSA-N [Mg].[Si] Chemical compound [Mg].[Si] MKPXGEVFQSIKGE-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000011342 resin composition Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、サイクリックＡＭ
Ｐ誘導体を含有する軟膏製剤に関し、更に詳しくは低温
条件下でも使用性が良好でかつ有効性にも優れた軟膏製
剤に関する。TECHNICAL FIELD The present invention relates to a cyclic AM
The present invention relates to an ointment preparation containing a P derivative, and more particularly, to an ointment preparation having good usability and excellent efficacy even under low temperature conditions.
【０００２】[0002]
【従来の技術】ブラクデシンナトリウムに代表されるサ
イクリックＡＭＰ誘導体は、褥瘡、熱傷などの皮膚潰瘍
の治療剤として有用であることが知られている（特開昭
６３−１０７９３５号公報）。そして、当該サイクリッ
クＡＭＰ誘導体を有効成分とする外用剤としては軟膏製
剤が知られており、軟膏製剤中におけるサイクリックＡ
ＭＰ誘導体の長期安定性を確保するため、サイクリック
ＡＭＰ誘導体を吸水性かつ乾燥性を有する基剤に配合
し、かつこれに無機高分子を配合する、一定のpHの塩を
配合する等の手段が行われている（特開平２−１４０９
号、同４−１３９１２９号及び同５−２７１０８０号公
報）。2. Description of the Related Art Cyclic AMP derivatives typified by bracdecin sodium are known to be useful as agents for treating skin ulcers such as pressure sores and burns (Japanese Patent Application Laid-Open No. 63-107935). An ointment preparation is known as an external preparation containing the cyclic AMP derivative as an active ingredient.
In order to ensure the long-term stability of the MP derivative, the cyclic AMP derivative is mixed with a water-absorbing and drying base, and an inorganic polymer is added thereto, and a salt having a constant pH is added. (Japanese Patent Laid-Open No. 2-1409)
Nos. 4-139129 and 5-271080).
【０００３】[0003]
【発明が解決しようとする課題】かかる手段により軟膏
製剤中のサイクリックＡＭＰ誘導体の分解防止について
は解決されたものの、これらの軟膏を低温条件下に保存
したとき軟膏が固くなり、チューブからの押し出し性、
ボトルからの取り出し性及び患部への塗布性等の点で十
分満足できないものであることが判明した。Although the prevention of the decomposition of the cyclic AMP derivative in the ointment preparation has been solved by such means, when these ointments are stored under low temperature conditions, the ointment becomes hard and is extruded from a tube. sex,
It was found that the resin composition was not sufficiently satisfactory in terms of taking out from a bottle and applicability to an affected part.
【０００４】従って、本発明の目的は、低温条件下でも
軟膏が固くならず、使用性の良好なサイクリックＡＭＰ
誘導体含有軟膏製剤を提供することにある。Accordingly, an object of the present invention is to provide a cyclic AMP which does not harden an ointment even under low temperature conditions and has good usability.
It is to provide a derivative-containing ointment preparation.
【０００５】[0005]
【課題を解決するための手段】そこで本発明者は上記課
題を解決すべく、軟膏基剤について種々検討してきた結
果、基剤として平均分子量の異なるポリエチレングリコ
ールを３種類以上組み合せて用いれば、有効成分である
サイクリックＡＭＰ誘導体の安定性、放出性を何ら低下
させることなく使用性が改善されることを見出し、本発
明を完成するに至った。In order to solve the above-mentioned problems, the present inventors have made various studies on ointment bases. As a result, if three or more polyethylene glycols having different average molecular weights are used in combination, it is effective. The inventors have found that the usability is improved without any decrease in the stability and release of the cyclic AMP derivative as a component, and the present invention has been completed.
【０００６】すなわち、本発明は、（ａ）サイクリック
ＡＭＰ誘導体と、（ｂ）平均分子量の異なる３種類以上
のポリエチレングリコールとを含有することを特徴とす
る軟膏製剤を提供するものである。That is, the present invention provides an ointment characterized by comprising (a) a cyclic AMP derivative and (b) three or more polyethylene glycols having different average molecular weights.
【０００７】[0007]
【発明の実施の形態】本発明における有効成分である
（ａ）サイクリックＡＭＰ（以下、ｃＡＭＰと略す）誘
導体としては、例えば、Ｎ6−モノアシルアデノシン−
３′，５′−環状リン酸、２′−Ｏ−モノアシルアデノ
シン−３′，５′−環状リン酸、Ｎ6，２′−Ｏ−ジア
シルアデノシン−３′，５′−環状リン酸又はこれらの
８−メルカプト、８−低級アルキルチオ、８−ベンジル
チオ、８−アミノ、８−ヒドロキシ、８−クロロもしく
は８−ブロモ置換体、８−ベンジルチオアデノシン−
３′，５′−環状リン酸もしくはそのＮ6−低級アルキ
ル置換体、又は８−メルカプトアデノシン−３′，５′
−環状リン酸等が挙げられる。これらのうち、ナトリウ
ム Ｎ6−２′−Ｏ−ジブチリルアデノシン−３′，
５′−サイクリックホスフェート（ブクラデシンナトリ
ウム、以下、ＤＢｃＡＭＰと略す）、ナトリウム２′−
Ｏ−ブチリルアデノシン−３′，５′−サイクリックホ
スフェート、ナトリウム Ｎ6−ブチリルアデノシン−
３′，５′−サイクリックホスフェート、ナトリウムア
デノシン−３′，５′−サイクリックホスフェート、８
−ベンジルチオ−Ｎ6−ブチリルアデノシン−３′，
５′−サイクリックホスフェート、８−ベンジルチオア
デノシン−３′，５′−サイクリックホスフェートが好
ましい。また、これらの化合物は単独でも、２種以上を
混合して使用することもできる。このうち、ＤＢｃＡＭ
Ｐを使用するのが最も好ましい。BEST MODE FOR CARRYING OUT THE INVENTION As the active ingredient in the present invention, (a) a cyclic AMP (hereinafter abbreviated as cAMP) derivative includes, for example, N 6 -monoacyl adenosine-
3 ', 5'-cyclic phosphate, 2'-O-monoacyl adenosine-3', 5'-cyclic phosphate, N 6, 2'-O-diacyl adenosine-3 ', 5'-cyclic phosphoric acid or These 8-mercapto, 8-lower alkylthio, 8-benzylthio, 8-amino, 8-hydroxy, 8-chloro or 8-bromo substituent, 8-benzylthioadenosine-
3 ', 5'-cyclic phosphate or its N 6 - lower alkyl substituted derivatives, or 8-mercapto adenosine-3', 5 '
-Cyclic phosphoric acid and the like. Of these, sodium N 6 -2′-O-dibutyryl adenosine-3 ′,
5'-cyclic phosphate (bucladecin sodium, hereinafter abbreviated as DBcAMP), sodium 2'-
O-butyryl adenosine-3 ', 5'-cyclic phosphate, sodium N 6 -butyryl adenosine-
3 ', 5'-cyclic phosphate, sodium adenosine-3', 5'-cyclic phosphate, 8
- benzylthio -N 6 - butyryl adenosine-3 ',
Preferred are 5'-cyclic phosphate and 8-benzylthioadenosine-3 ', 5'-cyclic phosphate. These compounds may be used alone or in combination of two or more. Of these, DBcAM
Most preferably, P is used.
【０００８】かかる（ａ）サイクリックＡＭＰ誘導体の
軟膏製剤中の配合量は、１回使用量との関係で適宜決定
すればよいが、通常０．１〜１５重量％、特に０．５〜
１０重量％が好ましい。[0008] The amount of the (a) cyclic AMP derivative in the ointment preparation may be appropriately determined in relation to the amount used once, but is usually 0.1 to 15% by weight, especially 0.5 to 15% by weight.
10% by weight is preferred.
【０００９】本発明に使用される（ｂ）平均分子量の異
なる３種類以上のポリエチレングリコールとしては、
（ｂ−１）平均分子量３０００〜５０００のポリエチレ
ングリコール、（ｂ−２）平均分子量３６０〜６５０の
ポリエチレングリコール及び（ｂ−３）平均分子量２０
０〜３５０のポリエチレングリコールの３種類の組み合
せがより好ましい。ここで（ｂ−１）のポリエチレング
リコールとしては、平均分子量４０００程度のものがよ
り好ましい。（ｂ−２）のポリエチレングリコールとし
ては平均分子量４００〜６００程度、特に平均分子量４
００程度のものが更に好ましい。また、（ｂ−３）のポ
リエチレングリコールとしては平均分子量３００程度の
ものがより好ましい。The (b) three or more polyethylene glycols having different average molecular weights used in the present invention include:
(B-1) polyethylene glycol having an average molecular weight of 3,000 to 5,000, (b-2) polyethylene glycol having an average molecular weight of 360 to 650, and (b-3) an average molecular weight of 20
More preferred are three combinations of 0-350 polyethylene glycol. Here, the polyethylene glycol of (b-1) preferably has an average molecular weight of about 4000. The polyethylene glycol of (b-2) has an average molecular weight of about 400 to 600, particularly 4
A value of about 00 is more preferable. The polyethylene glycol (b-3) preferably has an average molecular weight of about 300.
【００１０】これら平均分子量の異なる３種類のポリエ
チレングリコールの軟膏製剤中の配合量は、（ｂ−１）
のポリエチレングリコールが１〜５０重量％（特に１０
〜４０重量％）、（ｂ−２）のポリエチレングリコール
が１〜５０重量％（特に１０〜４０重量％）、（ｂ−
３）のポリエチレングリコールが５〜６０重量％（特に
２０〜５０重量％）であるのが好ましい。The amounts of these three types of polyethylene glycols having different average molecular weights in the ointment preparation are as follows: (b-1)
1 to 50% by weight (particularly 10%)
1 to 50% by weight (particularly 10 to 40% by weight), (b-2).
The polyethylene glycol of 3) is preferably 5 to 60% by weight (particularly 20 to 50% by weight).
【００１１】また、本発明の軟膏製剤には、サイクリッ
クＡＭＰ誘導体の安定化の目的で無機高分子を配合する
のが好ましく、かかる無機高分子としては、乾燥水酸化
アルミニウムゲル、合成ケイ素マグネシウム、ハイドロ
タルサイト等が挙げられる。これら無機高分子の配合量
は、軟膏製剤中、例えば０．１〜２０重量％、とりわけ
１〜２０重量％が適している。The ointment preparation of the present invention preferably contains an inorganic polymer for the purpose of stabilizing the cyclic AMP derivative. Examples of the inorganic polymer include a dry aluminum hydroxide gel, a synthetic silicon magnesium, Hydrotalcite and the like can be mentioned. The amount of the inorganic polymer to be blended is preferably, for example, 0.1 to 20% by weight, particularly preferably 1 to 20% by weight in the ointment preparation.
【００１２】また、本発明の軟膏製剤には、サイクリッ
クＡＭＰ誘導体のさらなる安定化を図る目的で、無機酸
塩、例えばリン酸塩を配合するのが好ましい。かかるリ
ン酸塩としては、リン酸アルカリ金属塩、特に無水リン
酸二水素ナトリウム等のリン酸ナトリウムが好ましい。
これら無機酸塩の配合量は、軟膏製剤中０．１〜２０重
量％、特に１〜２０重量％が好ましい。The ointment of the present invention preferably contains an inorganic acid salt, for example, a phosphate for the purpose of further stabilizing the cyclic AMP derivative. As such a phosphate, an alkali metal phosphate, particularly sodium phosphate such as anhydrous sodium dihydrogen phosphate is preferred.
The compounding amount of these inorganic acid salts is preferably 0.1 to 20% by weight, particularly preferably 1 to 20% by weight in the ointment preparation.
【００１３】更に、本発明の軟膏製剤には、界面活性
剤、抗酸化剤、保湿剤、防腐剤、着色剤、香料等を配合
することができる。Further, the ointment of the present invention may contain a surfactant, an antioxidant, a humectant, a preservative, a coloring agent, a fragrance and the like.
【００１４】また、本発明の軟膏製剤の０℃における硬
度は、使用性の点から０．００１〜２０ｇ／cm2 、特に
０．００１〜１０ｇ／cm2 が好ましい。[0014] The hardness at 0 ℃ ointment formulations of the present invention, 0.001 to 20 g / cm 2 from the viewpoint of usability, especially 0.001 to 10 g / cm 2 is preferred.
【００１５】本発明の軟膏製剤を製するには、通常の軟
膏の製造法に従えばよい。例えば、ポリエチレングリコ
ール等の軟膏基剤を６０〜７０℃程度で加温溶解させ冷
却して軟膏状にしたものに、ｃＡＭＰ誘導体及びその他
の成分の混合物を加え十分混合又は練合して分散又は溶
解させた後、冷却して軟膏製剤とする。混合又は練合
は、常法、例えば攪拌機スリーワンモーター（ＨＥＩＤ
ＯＮ社製）、ホモミキサー等により行われる。The preparation of the ointment preparation of the present invention may be carried out according to the usual ointment production method. For example, an ointment base such as polyethylene glycol is heated and dissolved at about 60 to 70 ° C. and cooled to form an ointment, and a mixture of the cAMP derivative and other components is added and sufficiently mixed or kneaded to be dispersed or dissolved. Then, the mixture is cooled to obtain an ointment preparation. Mixing or kneading may be carried out in a conventional manner, for example, using a three-one motor (HEID)
ON Company), a homomixer or the like.
【００１６】[0016]
【実施例】次に実施例を挙げて本発明を説明するが、本
発明はこれにより何ら制限されるものではない。Next, the present invention will be described with reference to examples, but the present invention is not limited thereto.
【００１７】実施例１ アジホモミクサー（特殊機加工業社製、Ｍ型）に窒素ガ
スバブリング下、ポリエチレングリコール４００を１９
９．２ｇと、ポリエチレングリコール３００を８００ｇ
加え攪拌し、更にポリエチレングリコール４０００を５
６０．０ｇ加え、調製液を７５℃まで加温しながら攪拌
溶解した。その後、無水リン酸二水素ナトリウム２０ｇ
を加え、約２０分間分散した。更に、予め、ブクラデシ
ンナトリウム６６．６ｇを３３４．０ｇのポリエチレン
グリコール４００中に溶解させ、更に乾燥水酸化アルミ
ニウムゲル２０ｇ及び香料０．２ｇを分散させた予製液
をアジホモミクサー内に投入し、調製液を５５℃まで上
昇させ、約２０分間攪拌し溶解又は分散させた後、攪拌
しながら製剤の温度を３７℃まで冷却して軟膏製剤を得
た。Example 1 Polyethylene glycol 400 was added to an Ajihomomixer (M type, manufactured by Tokushu Kikagyo Co., Ltd.) under nitrogen gas bubbling.
9.2 g and 800 g of polyethylene glycol 300
Add and stir, then add polyethylene glycol 4000 for 5
60.0 g was added, and the mixture was stirred and dissolved while being heated to 75 ° C. Then, anhydrous sodium dihydrogen phosphate 20g
Was added and dispersed for about 20 minutes. Further, 66.6 g of bucladecin sodium was previously dissolved in 334.0 g of polyethylene glycol 400, and a preliminarily prepared liquid in which 20 g of dried aluminum hydroxide gel and 0.2 g of fragrance were dispersed was poured into an adipomomixer. Then, the prepared solution was raised to 55 ° C., stirred for about 20 minutes to dissolve or disperse, and then the temperature of the formulation was cooled to 37 ° C. with stirring to obtain an ointment formulation.
【００１８】比較例１ アジホモミクサー（特殊機加工業社製、Ｍ型）に窒素ガ
スバブリング下、ポリエチレングリコール４００を１０
００ｇと、ポリエチレングリコール４０００を５６０．
０ｇ加え、調製液を７５℃まで加温しながら攪拌溶解し
た。その後、無水リン酸二水素ナトリウム２０ｇを加
え、約２０分間分散させた。更に、予め、ブクラデシン
ナトリウム６５．８ｇを３３４．０ｇのポリエチレング
リコール４００中に溶解させ、更に乾燥水酸化アルミニ
ウムゲル２０ｇ及び香料０．２ｇを分散させた予製液を
アジホモミクサー内に投入し、調製液の温度を５５℃ま
で上昇させ、約２０分間攪拌し、溶解又は分散させた
後、攪拌しながら４１℃まで冷却して軟膏製剤を得た。Comparative Example 1 10 polyethylene glycol 400 was added to an Ajihomomixer (M type manufactured by Tokushu Kikagyo Co., Ltd.) under nitrogen gas bubbling.
00g and polyethylene glycol 4000 for 560.
0 g was added, and the solution was stirred and dissolved while heating to 75 ° C. Thereafter, 20 g of anhydrous sodium dihydrogen phosphate was added and dispersed for about 20 minutes. Further, 65.8 g of bucladecin sodium was previously dissolved in 334.0 g of polyethylene glycol 400, and a pre-prepared liquid in which 20 g of dried aluminum hydroxide gel and 0.2 g of perfume were dispersed was poured into an adipomomixer. Then, the temperature of the preparation solution was raised to 55 ° C., and the mixture was stirred for about 20 minutes to dissolve or disperse, and then cooled to 41 ° C. with stirring to obtain an ointment preparation.
【００１９】試験例１ 実施例１の軟膏製剤と比較例１の軟膏製剤の０〜１０℃
における硬度を測定した。実施例及び比較例にて調製し
た軟膏製剤をそれぞれ、直径３７mm、高さ２０mmのプラ
スチック製の容器に、気泡が入らないように隙間なく充
填し、レオメーター（サン科学社製、ＣＲ２００Ｄ）の
試料台にのせ、試料台を１００mm／minの速度で上昇さ
せることにより、直径１０mm、長さ２０mmのアクリル製
の感圧軸を軟膏容器のほぼ中心部分に進入させて、軟膏
製剤の感圧軸接触面に与える重量を、軟膏製剤の硬度
（ｇ／cm2）として測定した。Test Example 1 0-10 ° C. of the ointment preparation of Example 1 and the ointment preparation of Comparative Example 1
Was measured for hardness. The ointment preparations prepared in Examples and Comparative Examples were each filled in a plastic container having a diameter of 37 mm and a height of 20 mm without gaps so as to prevent air bubbles, and a sample of a rheometer (manufactured by San Kagaku Co., CR200D) was prepared. By placing the sample stage on the stage and raising the sample stage at a speed of 100 mm / min, an acrylic pressure-sensitive shaft having a diameter of 10 mm and a length of 20 mm enters the substantially central portion of the ointment container and contacts the ointment formulation with the pressure-sensitive shaft. The weight given to the surface was measured as the hardness of the ointment preparation (g / cm 2 ).
【００２０】その結果、図１に示す如く、比較例１の軟
膏製剤は５℃以下では硬度が上昇するが、実施例１の軟
膏製剤は０℃でもほとんど硬度が上昇しないことがわか
る。As a result, as shown in FIG. 1, it can be seen that the hardness of the ointment of Comparative Example 1 is increased below 5 ° C., but that of the ointment of Example 1 hardly increases even at 0 ° C.
【００２１】試験例２ 比較例１の軟膏製剤中のポリエチレングリコール４００
の一部をポリエチレングリコール３００に置換し、当該
置換率（％）の異なる軟膏製剤を得た。得られた軟膏製
剤の０〜１０℃における硬度を測定し、ポリエチレング
リコール３００の置換率と硬度との関係を検討した。Test Example 2 Polyethylene glycol 400 in the ointment preparation of Comparative Example 1
Was replaced with polyethylene glycol 300 to obtain ointment preparations having different substitution rates (%). The hardness of the obtained ointment at 0 to 10 ° C. was measured, and the relationship between the substitution rate of polyethylene glycol 300 and the hardness was examined.
【００２２】得られた結果を図２に示す。図２から、ポ
リエチレングリコール４００の一部をポリエチレングリ
コール３００に置換すると低温、特に５℃以下での硬度
低下が抑制できることがわかる。FIG. 2 shows the obtained results. From FIG. 2, it can be seen that when a part of the polyethylene glycol 400 is replaced by the polyethylene glycol 300, the decrease in hardness at a low temperature, particularly at 5 ° C. or lower can be suppressed.
【００２３】試験例３ 実施例１又は比較例１の軟膏製剤をそれぞれチューブ
（２００ｇ）に充填した。このチューブを０〜９℃で冷
所保存してもらい、６箇所の病院で使用してもらい、チ
ューブからの押し出し性を官能評価した。Test Example 3 Each of the ointment preparations of Example 1 or Comparative Example 1 was filled in a tube (200 g). This tube was stored in a cold place at 0 to 9 ° C. and used at six hospitals, and the extrudability from the tube was sensory evaluated.
【００２４】その結果を表１及び表２に示す。なお、官
能評価は、次の４段階で行った。表中の数値は人数を示
す。 １：軽く押すと出る ２：普通に押すと出る ３：強く押すと出る ４：強く押しても出ないThe results are shown in Tables 1 and 2. The sensory evaluation was performed in the following four stages. The numbers in the table indicate the number of people. 1: Press lightly to get out 2: Press normally to get out 3: Press out harder 4: Get out even if pressed hard
【００２５】[0025]
【表１】 [Table 1]
【００２６】[0026]
【表２】 [Table 2]
【００２７】表１及び表２の結果より、比較例１の軟膏
は８℃以下で保存した場合、押し出し性が良くなかった
のに対し、実施例の軟膏は８℃以下の低温で保存しても
チューブからの押し出し性が良好であった。なお、この
結果は、３０ｇ入りチューブを用いた場合も同様であっ
た。From the results shown in Tables 1 and 2, the ointment of Comparative Example 1 was not extrudable when stored at 8 ° C. or lower, whereas the ointment of the Example was stored at a low temperature of 8 ° C. or lower. Also, the extrudability from the tube was good. The same result was obtained when a tube containing 30 g was used.
【００２８】試験例４ 実施例１又は比較例１の軟膏をそれぞれボトル（２００
ｇ）に充填した。このボトルを０〜９℃で冷所保存し、
試験例３と同様にしてボトルから軟膏ベラを用いての取
り出し性を官能評価した。Test Example 4 Each ointment of Example 1 or Comparative Example 1 was bottled (200
g). Store this bottle in a cool place at 0-9 ° C,
In the same manner as in Test Example 3, sensory evaluation was made on the removability from the bottle using an ointment spatula.
【００２９】その結果を表３及び表４に示す。なお、官
能評価は次の３段階で行った。表中の数値は人数を示
す。 １：取り出し易い ２：取り出し難い ３：取り出せないThe results are shown in Tables 3 and 4. The sensory evaluation was performed in the following three stages. The numbers in the table indicate the number of people. 1: Easy to remove 2: Difficult to remove 3: Cannot remove
【００３０】[0030]
【表３】 [Table 3]
【００３１】[0031]
【表４】 [Table 4]
【００３２】表３及び表４の結果より、比較例１の軟膏
は８℃以下で保存した場合、押し出し性が良くなかった
のに対し、実施例の軟膏は８℃以下の低温で保存しても
ボトルからの取り出し性が良好であった。From the results shown in Tables 3 and 4, the ointment of Comparative Example 1 had poor extrudability when stored at 8 ° C. or less, whereas the ointment of Example 1 was stored at a low temperature of 8 ° C. or less. Also had good take-out properties from the bottle.
【００３３】試験例５ 比較例１と実施例１の軟膏を用い、（１）２５℃、７５
％ＲＨ６ケ月保存時におけるＤＢｃＡＭＰの含量変化及
びpH変化、（２）ＤＢｃＡＭＰの放出性、（３）切傷に
対する治癒効果、及び（４）ウサギ耳介血流増加作用を
検討したところ、両軟膏間は同等であった。Test Example 5 Using the ointments of Comparative Example 1 and Example 1, (1) 25 ° C., 75
% RH and changes in pH during storage for 6 months, (2) release of DBcAMP, (3) healing effect on cuts, and (4) increase of rabbit ear blood flow. It was equivalent.
【００３４】[0034]
【発明の効果】本発明の軟膏製剤は８℃以下の低温条件
下でも硬度の上昇がなく、チューブからの押し出し性、
ボトルからの取り出し性が良好で、かつ創傷面などへの
塗布性も良好であるとともに、従来のサイクリックＡＭ
Ｐ含有軟膏と同様に有効である。The ointment preparation of the present invention does not increase in hardness even at a low temperature condition of 8 ° C. or less, and has extrudability from a tube,
It has good take-out properties from bottles and good applicability to wound surfaces, etc.
It is as effective as a P-containing ointment.
【図１】実施例１と比較例１の軟膏製剤の温度による硬
度変化を示す図である。FIG. 1 is a graph showing a change in hardness of an ointment preparation of Example 1 and Comparative Example 1 with temperature.
【図２】ポリエチレングリコール４００の一部をポリエ
チレングリコール３００に置換したときの置換率と軟膏
の低温条件下での硬度変化との関係を示す図である。FIG. 2 is a graph showing a relationship between a substitution rate when a part of polyethylene glycol 400 is replaced by polyethylene glycol 300 and a change in hardness of an ointment under a low temperature condition.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 ＦＩ // Ｃ０７Ｈ 19/213 Ｃ０７Ｈ 19/213 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 6 Identification code FI // C07H 19/213 C07H 19/213
Claims (4)
（ｂ）平均分子量の異なる３種類以上のポリエチレング
リコールとを含有することを特徴とする軟膏製剤。(1) a cyclic AMP derivative,
(B) An ointment preparation containing three or more kinds of polyethylene glycols having different average molecular weights.
−１）平均分子量３０００〜５０００のポリエチレング
リコール、（ｂ−２）平均分子量３６０〜６５０のポリ
エチレングリコール及び（ｂ−３）平均分子量２００〜
３５０のポリエチレングリコールの３種類である請求項
１記載の軟膏製剤。2. The method according to claim 1, wherein (b) the polyethylene glycol is (b)
-1) polyethylene glycol having an average molecular weight of 3000 to 5000, (b-2) polyethylene glycol having an average molecular weight of 360 to 650, and (b-3) average molecular weight of 200 to
3. The ointment preparation according to claim 1, wherein the ointment preparation comprises three types of 350 polyethylene glycols.
／cm2 である請求項１又は２記載の軟膏製剤。3. A hardness at 0 ° C. of 0.001 to 20 g.
The ointment preparation according to claim 1 or 2, wherein the ointment preparation is at least / cm 2 .
チレングリコールを１〜５０重量％、平均分子量３６０
〜６５０のポリエチレングリコールを１〜５０重量％、
平均分子量２００〜３５０のポリエチレングリコールを
５〜６０重量％含有するものである請求項２又は３記載
の軟膏製剤。4. A polyethylene glycol having an average molecular weight of 3,000 to 5,000, 1 to 50% by weight, and an average molecular weight of 360.
1 to 50% by weight of polyethylene glycol of
The ointment preparation according to claim 2 or 3, which contains 5 to 60% by weight of polyethylene glycol having an average molecular weight of 200 to 350.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04975699A JP4463337B2 (en) | 1998-02-26 | 1999-02-26 | Ointment formulation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10-45015 | 1998-02-26 | ||
| JP4501598 | 1998-02-26 | ||
| JP04975699A JP4463337B2 (en) | 1998-02-26 | 1999-02-26 | Ointment formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH11315035A true JPH11315035A (en) | 1999-11-16 |
| JP4463337B2 JP4463337B2 (en) | 2010-05-19 |
Family
ID=26384966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP04975699A Expired - Lifetime JP4463337B2 (en) | 1998-02-26 | 1999-02-26 | Ointment formulation |
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| Country | Link |
|---|---|
| JP (1) | JP4463337B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010198626A (en) * | 2003-04-23 | 2010-09-09 | Yuyama Manufacturing Co Ltd | Medicine management system |
| JP2013510611A (en) * | 2009-11-12 | 2013-03-28 | ボンアリベ ビオマテリアルス オサケユイチア | Embedding paste and its use |
-
1999
- 1999-02-26 JP JP04975699A patent/JP4463337B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010198626A (en) * | 2003-04-23 | 2010-09-09 | Yuyama Manufacturing Co Ltd | Medicine management system |
| JP2013510611A (en) * | 2009-11-12 | 2013-03-28 | ボンアリベ ビオマテリアルス オサケユイチア | Embedding paste and its use |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4463337B2 (en) | 2010-05-19 |
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