JP3310994B2 - Allergy treatment - Google Patents
Allergy treatmentInfo
- Publication number
- JP3310994B2 JP3310994B2 JP18827991A JP18827991A JP3310994B2 JP 3310994 B2 JP3310994 B2 JP 3310994B2 JP 18827991 A JP18827991 A JP 18827991A JP 18827991 A JP18827991 A JP 18827991A JP 3310994 B2 JP3310994 B2 JP 3310994B2
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- JP
- Japan
- Prior art keywords
- hyaluronic acid
- present
- allergic
- nasal
- hyaluronic
- Prior art date
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、新規なアレルギー治療
剤に関するものであり、さらに詳しくは、ヒアルロン酸
及び／又は生体内投与可能なヒアルロン酸非毒性塩（以
下、総称してヒアルロン酸類という）を含有する優れた
抗アレルギー作用を有する治療剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel agent for treating allergies, and more particularly to non-toxic salts of hyaluronic acid and / or hyaluronic acid which can be administered in vivo (hereinafter collectively referred to as hyaluronic acids). And a therapeutic agent having an excellent antiallergic effect.
【０００２】[0002]
【従来の技術】従来、気管支喘息、アトピー性皮膚炎、
花粉症等に代表されるアレルギー疾患の治療剤には、免
疫抑制剤、ホルモン剤等がある。また、関節症治療剤と
して広く用いられているヒアルロン酸を抗アレルギー製
剤に用いる例として、特開平２−３２０１３号公報に
は、ヒアルロン酸と活性薬剤を含有する点鼻剤が開示さ
れている。2. Description of the Related Art Conventionally, bronchial asthma, atopic dermatitis,
Examples of therapeutic agents for allergic diseases such as hay fever include immunosuppressants, hormonal agents and the like. As an example of using hyaluronic acid, which is widely used as a therapeutic agent for arthrosis, in an antiallergic preparation, JP-A-2-32013 discloses a nasal drop containing hyaluronic acid and an active drug.
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、これら
のアレルギー疾患治療剤には、副作用があり、またいず
れも十分な効能がないという欠点があった。また、ヒア
ルロン酸を抗アレルギー製剤に用いる例では、ヒアルロ
ン酸が強い保水性高分子マトリックスである特徴を利用
して薬物の徐放効果と、たれを生じにくい点鼻剤を指向
したものであり、活性薬剤の例として抗アレルギー薬も
示されてはいるがヒアルロン酸単独でのアレルギーに対
する効果は全く検討されていない。さらに、ヒアルロン
酸の薬理作用に関しても未だ十分に知られていない。However, these remedies for allergic diseases have the disadvantage that they have side effects and are not sufficiently effective. Also, in the case of using hyaluronic acid in an antiallergic preparation, hyaluronic acid takes advantage of its strong water-retaining polymer matrix, and is intended for a drug release effect and a nasal drop that does not easily cause sagging, Although an antiallergic drug is shown as an example of an active drug, the effect of hyaluronic acid alone on allergy has not been studied. Furthermore, the pharmacological action of hyaluronic acid is not yet sufficiently known.
【０００４】本発明は、従来のアレルギー治療剤とは異
なるタイプの抗アレルギー作用を有する治療剤を提供す
ることを目的とするものであり、ヒアルロン酸類それ自
身の抗アレルギー活性に関しては、本発明によって初め
て見い出されたものである。本発明者等は、鋭意研究を
重ねた結果、ヒアルロン酸類を有効成分として含有する
アレルギー治療剤が従来のアレルギー治療剤と異なる治
療剤であることを見い出し、本発明を完成するに至っ
た。An object of the present invention is to provide a therapeutic agent having a different type of antiallergic activity from conventional allergic therapeutic agents. The antiallergic activity of hyaluronic acid itself is determined by the present invention. It was discovered for the first time. As a result of intensive studies, the present inventors have found that an allergy therapeutic agent containing a hyaluronic acid as an active ingredient is a different therapeutic agent from conventional allergy therapeutic agents, and completed the present invention.
【０００５】[0005]
【課題を解決するための手段】すなわち本発明は、
（１）ヒアルロン酸及び／又はヒアルロン酸非毒性塩を
有効成分として０．０１〜１０重量％含有し、皮膚塗布
剤として用いられる皮膚のアレルギー疾患治療剤であ
る。That is, the present invention provides:
(1) A therapeutic agent for skin allergic diseases which contains 0.01 to 10% by weight of hyaluronic acid and / or a non-toxic salt of hyaluronic acid as an active ingredient, and is used as a skin coating agent.
【０００６】以下、さらに本発明について詳しく説明す
る。アレルギー反応で炎症を惹起させる主役の肥満細
胞、好塩基球は、ヒアルロン酸のレセプターを有してい
ることが明かとなっている。(Int Arch Allergy Appl I
mmunol, 91,198,(1990)) 本発明者らは、上記の事実を
踏まえ、ヒアルロン酸類の抗アレルギー作用につき鋭意
検討した結果、ヒアルロン酸類が肥満細胞、好塩基球に
結合することで、細胞とイムノグロブリン間の結合及び
イムノグロブリンの抗原による架橋が阻害され、肥満細
胞からの化学伝達物質の遊離が減少し、その結果、アレ
ルギーによる炎症を迅速に抑制する可能性に着目し鋭意
検討した。Hereinafter, the present invention will be described in more detail. It has been revealed that mast cells and basophils, which play a leading role in causing inflammation in allergic reactions, have a receptor for hyaluronic acid. (Int Arch Allergy Appl I
mmunol, 91, 198, (1990)) Based on the above facts, the present inventors have conducted intensive studies on the anti-allergic effects of hyaluronic acids, and found that hyaluronic acids bind to mast cells and basophils, and cells and We focused on the possibility that the binding between globulins and the cross-linking of immunoglobulins by antigens were inhibited, the release of chemical messengers from mast cells was reduced, and as a result, inflammation due to allergies could be suppressed promptly, and intensive studies were conducted.
【０００７】従来の抗アレルギー剤には、肥満細胞の膜
安定化効果によるヒスタミンの分泌抑制剤、ロイコトリ
エン、ＰＡＦ、ヒスタミン等の合成阻害剤、化学伝達物
質放出を抑制する副腎皮質ホルモン、抗原投与による減
感療法剤、変調療法としての金製剤等があるが、本発明
によるヒアルロン酸類の抗アレルギー効果は従来のもの
と全く異なったタイプのものである。本発明で用いるヒ
アルロン酸類は、鶏冠、水晶体、臍の緒などからの抽出
物又はストレプトコッカス（Ｓｔｒｅｐｔｏｃｏｃｃｕ
ｓ）属のヒアルロン酸生産菌の培養物由来のもの等の起
源をとわず利用できる。ヒアルロン酸は元来、ヒトを含
めた全ての動物の体内で合成され、体の各部でそれぞれ
重要な機能を果たしている生体物質であり、眼科及び整
形外科分野等で医薬品として利用される程、安全性の高
いムコ多糖類の一種である。Conventional antiallergic agents include inhibitors of histamine secretion due to mast cell membrane stabilizing effect, inhibitors of synthesis of leukotriene, PAF, histamine, etc., corticosteroids which suppress the release of chemical messengers, and antigen administration. Although there are a desensitizing agent, a gold preparation as a modulation therapy, and the like, the antiallergic effect of the hyaluronic acid according to the present invention is of a completely different type from the conventional one. The hyaluronic acids used in the present invention are extracts from cockscomb, lens, umbilical cord, etc. or Streptococcus.
s) It can be used irrespective of its origin, such as those derived from cultures of hyaluronic acid-producing bacteria of the genus. Originally, hyaluronic acid is a biological substance that is synthesized in the body of all animals including humans and plays an important role in each part of the body, and is safe enough to be used as a pharmaceutical in ophthalmology and orthopedic fields. It is a kind of mucopolysaccharide with high potency.
【０００８】本発明に用いられるヒアルロン酸類は、ヒ
アルロン酸、ヒアルロン酸非毒性塩、又はヒアルロン酸
とヒアルロン酸非毒性塩の混合物を包含している。ヒア
ルロン酸類は、遊離の形でもよく又その塩でもよく例え
ば、ナトリウム塩、カリウム塩、カルシウム塩等が挙げ
られる。[0008] The hyaluronic acids used in the present invention include hyaluronic acid, non-toxic salts of hyaluronic acid, or a mixture of hyaluronic acid and non-toxic salts of hyaluronic acid. The hyaluronic acids may be in a free form or a salt thereof, and examples thereof include a sodium salt, a potassium salt and a calcium salt.
【０００９】本発明に用いるヒアルロン酸類の濃度は、
その分子量に応じ粘度、流動性が異なるため一概には言
えず、またその剤形、使用法によって異なるが、点鼻剤
として用いるには、０．０１〜２重量％、点眼剤として
用いるには０．０００１〜５重量％、皮膚、粘膜用塗布
剤として用いるには、０．０１〜１０重量％、口腔、咽
頭用の噴射塗布剤として用いるには、０．０１〜５重量
％の範囲で用いるのが好ましい。また、ヒアルロン酸類
を粉末のまま、種々な形態で用いてもよい。本発明の製
剤形態は、固体または液体の形態、さらにはゲル状の半
液体の形態にすることができる。本発明に用いるヒアル
ロン酸類の分子量には特に制限はないが、分子量１万〜
５００万であることが好ましい。The concentration of the hyaluronic acids used in the present invention is as follows:
Viscosity and fluidity are different depending on the molecular weight, so it cannot be said unconditionally, and it varies depending on the dosage form and usage. However, when used as a nasal drop, 0.01 to 2% by weight, when used as an eye drop, 0.0001 to 5% by weight, 0.01 to 10% by weight for use as an application for skin and mucous membrane, 0.01 to 5% by weight for use as a spray application for oral cavity and pharynx It is preferably used. Further, the hyaluronic acids may be used in various forms as powder. The formulation of the present invention can be in the form of a solid or liquid, or a semi-liquid gel. Although the molecular weight of the hyaluronic acids used in the present invention is not particularly limited, the molecular weight is 10,000 to
Preferably it is 5 million.
【００１０】ヒアルロン酸類は、単独でアレルギー治療
剤として用いることができるがさらに抗アレルギー効果
を高めるため、例えば作用メカニズムの異なる他の抗ア
レルギー活性を有する薬と混合して使用、または併用す
ることも可能である。他の抗アレルギー活性を有する薬
としては、例えば、デキサメタゾン、ベタメタゾン、酢
酸メチルプレドニゾロン、プレドニゾロン、リン酸ヒド
ロコルチゾンナトリウム、コハク酸ヒドロコルチゾンナ
トリウム等のステロイド剤、塩酸ジフェンヒドラミン、
塩酸ホモクロルシクリジン、フマル酸クレマスチン、マ
レイン酸クロルフェニラミン等の抗ヒスタミン剤、グリ
チルリチン、トラネキサム酸、アゼラスチン、クロモグ
ルク酸ナトリウム、アンレキサノクス等が挙げられる
が、これらによって何等制限を受けるものではない。[0010] Hyaluronic acids can be used alone as a therapeutic agent for allergy, but may be used in combination with other drugs having different anti-allergic activities having different action mechanisms or used in combination to further enhance the antiallergic effect. It is possible. Other drugs having anti-allergic activity, for example, dexamethasone, betamethasone, methylprednisolone acetate, prednisolone, hydrocortisone sodium phosphate, steroids such as sodium hydrocortisone sodium succinate, diphenhydramine hydrochloride,
Examples include antihistamines such as homochlorcyclidine hydrochloride, clemastine fumarate, and chlorpheniramine maleate, glycyrrhizin, tranexamic acid, azelastine, sodium cromoglucate, amlexanox, and the like, but are not limited thereto.
【００１１】[0011]
【実施例】以下、実施例を揚げて本発明について具体的
に説明するが、本発明は以下の実施例に限定されるもの
ではない。尚、濃度は特に記載のない限り重量％を示
す。実施例１ ＳＤ系雌ラットをエーテル麻酔下放血致死させ、腹腔内
にＨＢＳＳ（Ｈａｎｋｓ Ｂａｌａｎｓ ｓａｌｔ ｓ
ｏｌｕｔｉｏｎ）を注入し、マッサージした後、腹腔内
細胞を採取、洗浄後、ラット抗ＯＶＡ血清（卵白アルブ
ミン）で３７℃２時間インキュベートした後、遠心して
フリーの抗ＯＶＡ血清を取り除き、ＨＢＳＳで１〜３×
１０6 細胞／ｍｌに調整し、実験に供した。この細胞と
ヒアルロン酸ナトリウム（培養品、分子量１８０万）を
共に３７℃、２０分間恒温槽に放置した後、１０ｍｇ／
ｍｌＯＶＡで刺激し、肥満細胞からの遊離ヒスタミン量
を測定した。肥満細胞からの全ヒスタミン量は、２％ト
ライトンＸ−１００で細胞を破壊して測定した。ヒアル
ロン酸ナトリウムのラット腹腔肥満細胞からのヒスタミ
ン遊離に対する抑制率の結果を表１に示した。Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited to the following examples. In addition, the concentration indicates weight% unless otherwise specified. Example 1 An SD female rat was sacrificed by exsanguination under ether anesthesia, and HBSS (Hanks Balans salt s.
injection, massaged, intraperitoneal cells were collected, washed, incubated with rat anti-OVA serum (ovalbumin) at 37 ° C. for 2 hours, centrifuged to remove free anti-OVA serum, and HBSS was added. 3x
It was adjusted to 10 6 cells / ml and used for the experiment. After leaving the cells and sodium hyaluronate (cultured product, molecular weight 1.8 million) together in a thermostat at 37 ° C for 20 minutes, 10 mg /
After stimulation with mlOVA, the amount of free histamine from mast cells was measured. Total histamine levels from mast cells were determined by disrupting cells with 2% Triton X-100. Table 1 shows the results of the inhibition rate of sodium hyaluronate against histamine release from rat peritoneal mast cells.
【表１】 [Table 1]
【００１２】実施例２ Ｗｉｓｔｅｒ系雄ラット（４週令）に２０ｍｇ／ｍｌの
卵白アルブミン（ＯＶＡ）にｃｏｍｐｌｅｔｅ Ｆｒｅ
ｕｎｄ' ｓ ａｄｊｕｖａｎｔを加え肢皮下に注射して
感作した。その後、２週間おきに２回追加免疫を行いさ
らに１週間たった能動感作ラットを用いた。ラットは頭
部を外に突き出させて筒状チャンバーに固定した。差圧
トランジューサーを装着したアダプターを頭部にかぶ
せ、呼吸量と呼吸数を測定し、ペンレコーダ上に記録で
きるようにした。固定した動物は５分間静置して呼吸の
乱れが鎮静したのを確認した後、０．５％のヒアルロン
酸ナトリウム（鶏冠抽出品、分子量１５０万）の生理食
塩水溶液を両鼻腔に２０μｌづつ点鼻した。１０分後に
呼吸を測定し、鎮静していることを確認した。引続き誘
発は３ｍｇ／ｍｌのＯＶＡの生理食塩水溶液を両鼻腔に
１０μｌづつ点鼻して行った。鼻症状（鼻汁、鼻閉）は
抗原誘発直後に出現してくるので、点鼻後１０分間の観
察で検定した。なお対照群としては本発明の治療剤の代
わりに生理食塩水２０μｌ点鼻した。 Example 2 Male Wister rats (4 weeks old) were mixed with 20 mg / ml ovalbumin (OVA) in complete Fre
Und's adjuvant was added and injected subcutaneously in the limb for sensitization. Thereafter, booster immunization was performed twice every two weeks, and active sensitized rats one week later were used. Rats were fixed in a cylindrical chamber with their heads protruding out. An adapter equipped with a differential pressure transducer was placed over the head, and the respiratory volume and respiratory rate were measured and recorded on a pen recorder. The fixed animal was allowed to stand for 5 minutes to confirm that respiratory disturbance had subsided, and then a 20% aqueous saline solution of 0.5% sodium hyaluronate (cotyledon extract, molecular weight 1.5 million) was applied to both nasal cavities. I nose. Ten minutes later, respiration was measured, and it was confirmed that the patient was sedated. Subsequently, induction was performed by instilling 10 μl of a 3 mg / ml saline solution of OVA into both nasal cavities. Nasal symptoms (nasal discharge, nasal congestion) appeared immediately after the antigen induction, and were examined by observation 10 minutes after nasal instillation. As a control group, 20 μl of saline was instilled in place of the therapeutic agent of the present invention.
【００１３】対照群（６例）では反応誘発後１０分以内
に、４例で過鼻汁を伴う呼吸数の低下、それに引き続く
呼吸困難（全身症状としての「あばれ」）の出現（これ
を「鼻アレルギー症状発現」の指標とした）を観察し
た。この対照群に対し、本発明のヒアルロン酸ナトリウ
ム投与群（５例）中２例は呼吸は全く変化しなかった
が、残り３例もやや鼻汁過多で、呼吸数の減少はあった
が、対照群で観察された「あばれ」には至らなかった。
以上の結果よりヒアルロン酸点鼻薬の抗アレルギー作用
が確認された。In the control group (6 cases), within 10 minutes after the induction of the reaction, in 4 cases, a decrease in respiratory rate accompanied by nasal discharge and subsequent dyspnea ("abnormality" as a systemic symptom) (referred to as "nasal") Was used as an index of "allergic episodes". In contrast to this control group, 2 of the 5 groups of the sodium hyaluronate administration group of the present invention did not show any change in respiration, but the remaining 3 cases had a slight excess of nasal discharge and a decrease in respiratory rate. It did not lead to the "abuse" observed in the group.
From the above results, the antiallergic effect of the hyaluronic acid nasal drops was confirmed.
【００１４】実施例３ Ｍｏｔａの方法（Ｌｉｆｅ Ｓｅｉ．，１２・９１７
（１９６３））によって作成した卵白アルブミンに対す
る抗血清（ＰＣＡ力価、１：３２）を用い、Ｉｓｏらの
方法（ＯｐｈｔａｌｍｉｃＲｅｓ.,１２・９（１９８
０））に準じてヒアルロン酸類のラット結膜でのアレル
ギー反応抑制効果を検討した。なおヒアルロン酸ナトリ
ウム（培養品、分子量１７０万）は生理食塩液に溶解
後、ｐＨを７．５に調整したものを点眼液とし、抗原チ
ャレンジの５分及び１５分前に１０μｌ点眼した。結果
を表２に示した。 Example 3 The method of Mota (Life Sei., 12.917)
(1963)), and using the antiserum against ovalbumin (PCA titer, 1:32), the method of Iso et al. (Ophthalmic Res., 12.9 (198)
0)), the inhibitory effect of hyaluronic acids on allergic reaction in rat conjunctiva was examined. After dissolving sodium hyaluronate (cultured product, molecular weight: 1.7 million) in physiological saline, the solution adjusted to pH 7.5 was used as an ophthalmic solution, and 10 μl was instilled 5 minutes and 15 minutes before the antigen challenge. The results are shown in Table 2.
【表２】 実施例４ ＳＤラットの皮膚の一部に予め２％ヒアルロン酸ナトリ
ウム溶液（培養品、分子量１００万）を塗布、他のラッ
トに卵白アルブミン（ＯＶＡ）を免疫することで作製し
た抗ＯＶＡ血清を２倍希釈系列で希釈したものを塗布し
た部分と塗布していない部分の皮内に０．１ｍｌずつ投
与、４時間後に色素添加ＯＶＡ溶液（ＯＶＡ２ｍｇ／ｍ
ｌ０．５ｍｌと１％エバンスブルー０．５ｍｌの混合溶
液）を尾静脈より投与しＰＣＡ反応を惹起させた。屠殺
後、表皮を剥離して漏出色素量を測定した。ヒアルロン
酸ナトリウム塗布により４８．２％のＰＣＡ抑制が認め
られた。この結果よりヒアルロン酸塗布剤の抗アレルギ
ー作用が確認された。[Table 2] Example 4 An anti-OVA serum prepared by applying a 2% sodium hyaluronate solution (cultured product, molecular weight: 1,000,000) to a part of the skin of an SD rat in advance and immunizing other rats with ovalbumin (OVA) was used. 0.1 ml each of the diluted and serially diluted series was applied to the inside of the skin and the uncoated part, and 4 hours later, the dye-added OVA solution (OVA 2 mg / m2)
(a mixed solution of 0.5 ml of 1% and 0.5 ml of 1% Evans blue) was administered via the tail vein to induce a PCA reaction. After sacrifice, the epidermis was peeled off and the amount of the leaked pigment was measured. PCA suppression of 48.2% was observed by the application of sodium hyaluronate. From these results, the anti-allergic effect of the hyaluronic acid application was confirmed.
【００１６】実施例５ ヒスタミン閾値を測定したモルモットを１０匹用意し、
そのうち８匹に先に用意したＯＶＡ特異的ＩｇＥを含む
血清を１ｍｌづつ静注し、残りの２匹に生理食塩水を１
ｍｌづつ静注した。８日後、４匹のモルモットには咽頭
に１％ヒアルロン酸ナトリウム（培養品、分子量１０
万）０．５ｍｌを噴射塗布し、残り４匹には生理食塩水
を噴射塗布した後すべてのモルモットに２ｍｇ／ｍｌの
ＯＶＡ生理食塩水溶解液を１分間吸入させ（耐えられな
い場合は途中で中止）、その際のモルモットの呼吸抵
抗、呼吸パターンを経時的に観察した。ＩｇＥ血清を静
注した８匹のうちヒアルロン酸ナトリウムを塗布した群
は対照群に比べ呼期の延長が著しく抑制され、呼吸抵抗
の上昇も抑制された。この結果よりヒアルロン酸噴射塗
布剤の抗アレルギー作用が確認された。 Example 5 Ten guinea pigs whose histamine threshold was measured were prepared.
Eight of them were intravenously injected with 1 ml of the serum containing OVA-specific IgE prepared above, and the other two were given 1 ml of physiological saline.
The solution was intravenously injected by ml. Eight days later, four guinea pigs had 1% sodium hyaluronate (culture, molecular weight 10
10,000 ml) was spray-applied, and the remaining 4 animals were spray-applied with saline, and then all guinea pigs were inhaled with a 2 mg / ml saline solution of OVA for 1 minute. Discontinuation), and the respiratory resistance and respiratory pattern of the guinea pig were observed over time. Among the eight animals to which IgE serum was intravenously injected, the group to which sodium hyaluronate was applied was significantly suppressed in prolongation of expiration and the increase in respiratory resistance as compared with the control group. From these results, the anti-allergic effect of the hyaluronic acid spray application was confirmed.
【００１７】[0017]
【発明の効果】本発明に従い、作製されたアレルギー治
療剤は副作用がなく、また、従来のアレルギー治療剤と
異なった作用で抗アレルギー効果を発現する。According to the present invention, the allergic therapeutic agent produced according to the present invention has no side effects, and exhibits an antiallergic effect by an action different from that of conventional allergic therapeutic agents.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭62−255428（ＪＰ，Ａ) 特開 平２−53728（ＪＰ，Ａ) 応用薬理，Ｖｏｌ．28，Ｎｏ．６, （1984）ｐ．1123−1135 (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 31/728 A61K 9/08 A61P 37/08 ＣＡ（ＳＴＮ)──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-62-255428 (JP, A) JP-A-2-53728 (JP, A) Applied Pharmacology, Vol. 28, No. 6, (1984) p. 1123-1135 (58) Field surveyed (Int. Cl. 7 , DB name) A61K 31/728 A61K 9/08 A61P 37/08 CA (STN)
Claims (1)
毒性塩を有効成分として０．０１〜１０重量％含有し、
皮膚塗布剤として用いられる皮膚のアレルギー疾患治療
剤。Claims: 1. An anti-hyaluronic acid and / or a non-toxic salt of hyaluronic acid is contained as an active ingredient in an amount of 0.01 to 10% by weight ,
A therapeutic agent for skin allergic diseases used as a skin coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18827991A JP3310994B2 (en) | 1991-07-03 | 1991-07-03 | Allergy treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18827991A JP3310994B2 (en) | 1991-07-03 | 1991-07-03 | Allergy treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05320055A JPH05320055A (en) | 1993-12-03 |
| JP3310994B2 true JP3310994B2 (en) | 2002-08-05 |
Family
ID=16220874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18827991A Expired - Fee Related JP3310994B2 (en) | 1991-07-03 | 1991-07-03 | Allergy treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3310994B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008290998A (en) * | 2007-05-28 | 2008-12-04 | Seikagaku Kogyo Co Ltd | Therapeutic agent for i type allergic disease |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1263394B (en) * | 1993-07-30 | 1996-08-05 | Fidia Advanced Biopolymers Srl | PHARMACEUTICAL COMPOSITIONS FOR TOPICAL USE BASED ON HYALURONIC ACID AND ITS DERIVATIVES |
| US20020055488A1 (en) * | 2000-09-21 | 2002-05-09 | Wessels Michael R. | Prevention and treatment of streptococcal and staphylococcal infection |
| FR2847818B1 (en) * | 2002-11-28 | 2008-04-04 | Agro Ind Rech S Et Dev Ard | PHARMACEUTICAL COMPOSITION BASED ON HYALURONIC ACID |
| DE10360425A1 (en) * | 2003-12-19 | 2005-07-28 | Ursapharm Arzneimittel Gmbh & Co. Kg | Compositions containing hyaluronic acid or its derivatives as sole active agent, useful for topical treatment of ophthalmological or rhinological allergic complications |
| DE102004002001A1 (en) * | 2004-01-14 | 2005-08-11 | Reinmüller, Johannes, Dr.med. | Agent for the treatment of inflammatory diseases |
| JP2006008516A (en) * | 2004-06-21 | 2006-01-12 | Nippon Kenko Kagaku Kenkyu Center:Kk | Ointment for preventing nostril pollinosis and stick ointment for preventing nostril pollinosis |
| JP4889206B2 (en) * | 2004-07-01 | 2012-03-07 | 有限会社 シーバイオン | Macrophage activator having IL-12 production inducing activity |
| EP2070518A2 (en) | 2006-07-25 | 2009-06-17 | Osmotica Corp. | Ophthalmic solutions |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4808576A (en) * | 1986-04-28 | 1989-02-28 | Mobay Corporation | Remote administration of hyaluronic acid to mammals |
| JP2504788B2 (en) * | 1987-11-10 | 1996-06-05 | 東京田辺製薬株式会社 | Aqueous formulation of 9-methyl-3- (1H-tetrazol-5-yl) -4H-pyrido [1,2-a] pyrimidin-4-one potassium salt |
| US4880813A (en) * | 1988-07-22 | 1989-11-14 | Baker Cummins Pharmaceuticals, Inc. | Method of treatment for allergic rhinitis |
| JPH02138215A (en) * | 1988-08-05 | 1990-05-28 | Dai Ichi Seiyaku Co Ltd | Antiallergic and anti-inflammatory agent |
| JPH0253728A (en) * | 1988-08-17 | 1990-02-22 | Mieko Nakamura | Medicine for prevention of snore |
| JP2769584B2 (en) * | 1990-06-04 | 1998-06-25 | 参天製薬株式会社 | Antiallergic agent for topical administration |
-
1991
- 1991-07-03 JP JP18827991A patent/JP3310994B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 応用薬理，Ｖｏｌ．２８，Ｎｏ．６，（１９８４）ｐ．１１２３−１１３５ |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008290998A (en) * | 2007-05-28 | 2008-12-04 | Seikagaku Kogyo Co Ltd | Therapeutic agent for i type allergic disease |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05320055A (en) | 1993-12-03 |
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