JPH06340549A - Therapeutic agent for feline respiratory organ disease and therapeutic method using the therapeutic agent - Google Patents

Therapeutic agent for feline respiratory organ disease and therapeutic method using the therapeutic agent

Info

Publication number
JPH06340549A
JPH06340549A JP6095542A JP9554294A JPH06340549A JP H06340549 A JPH06340549 A JP H06340549A JP 6095542 A JP6095542 A JP 6095542A JP 9554294 A JP9554294 A JP 9554294A JP H06340549 A JPH06340549 A JP H06340549A
Authority
JP
Japan
Prior art keywords
huifn
therapeutic agent
cats
human interferon
respiratory diseases
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
Application number
JP6095542A
Other languages
Japanese (ja)
Other versions
JP3640980B2 (en
Inventor
Naokatsu Miwa
尚克 三輪
Taketoshi Tamura
剛捷 田村
Hitoshi Murasaki
等 村▲さき▼
Masakazu Mihashi
正和 三橋
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hayashibara Seibutsu Kagaku Kenkyujo KK
Original Assignee
Hayashibara Biochemical Laboratories Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hayashibara Biochemical Laboratories Co Ltd filed Critical Hayashibara Biochemical Laboratories Co Ltd
Priority to JP09554294A priority Critical patent/JP3640980B2/en
Publication of JPH06340549A publication Critical patent/JPH06340549A/en
Application granted granted Critical
Publication of JP3640980B2 publication Critical patent/JP3640980B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Abstract

PURPOSE:To obtain a feline respiratory disease therapeutic agent exhibiting remarkable effects, even when administered through routes except veins, and capable of reducing the labor load of a person on the therapeutic duty and the economical load of an owner. CONSTITUTION:The characteristic of this feline respiratory organ disease therapeutic agent comprises containing as an active ingredient an interferon produced by a microorganismic or animal cell into which an HuIFN-related gene collected from cells originated from human has been introduced. The HuIFN can mainly be classified into three kind types consisting of HuIFN-alpha, HuIFN-beta and HuIFN-gamma on the basis of antigenicity. Only one kind type of the HuIFN may be used, or a combination of different kind types of the HuIFN may be used. Even when any HuIFN is used, it is desirable to use the HuIFN having as high specific activity as possible. When orally administered, a partially or wholly purified product having a specific activity of approximately 10<5> international units/mg of protein is desirable, and when parenterally administered, a purified product having a specific activity of approximately 10<7> international units/mg of protein is desirable.

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【産業上の利用分野】この発明は、ネコを対象とする動
物医薬、とりわけ、ヒトインターフェロン(以下、「H
uIFN」と略記することがある。)を有効成分とする
ネコの呼吸器疾患治療剤に関するものである。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to veterinary medicine for cats, especially human interferon (hereinafter referred to as "H").
It may be abbreviated as "uIFN". ) Is an active ingredient for treating respiratory diseases in cats.

【0002】[0002]

【従来の技術】近年、生活が豊かになるに伴い、心の豊
さを愛玩動物に求める人が増えている。愛玩動物の中で
も、とりわけ、ネコは、古来より、イヌと並んで最も人
気のある愛玩動物であり、長年に亙る品種改良により多
種多様な品種が作出され、現在では驚くほど高価な品種
も出現するようになった。前述のような昨今の傾向か
ら、家庭で飼育されるネコの数も驚異的に増加し、それ
に伴なって、動物病院に持ち込まれるネコの数が急増し
ている。
2. Description of the Related Art In recent years, with the enrichment of life, more and more people are demanding the compassion for pet animals. Among pet animals, cats have been one of the most popular pet animals along with dogs since ancient times, and a wide variety of breeds have been created by breeding over many years, and nowadays a surprisingly expensive breed also appears. It became so. Due to the recent tendency as described above, the number of cats housed at home is also increasing dramatically, and the number of cats brought to veterinary hospitals is rapidly increasing accordingly.

【0003】動物病院で取り扱われるネコは、外傷や骨
折などにより外科的治療を必要とするものを除けば、さ
まざまな感染症、とりわけ、ネコの呼吸器疾患、いわゆ
る「ネコ風邪」に罹患して持ち込まれるケースが多発し
ている。ネコ風邪の主因は気道感染ウイルスと考えられ
ており、ネコがこれに感染すると、多くの場合、咳、鼻
水、流涎、発熱、上部気道炎、肺炎、口内炎、舌炎、結
膜炎、顆粒性腺炎、舌部潰瘍、鼻端部潰瘍、全身性皮膚
潰瘍、鼻甲介部潰瘍、下痢、嘔吐、食欲減退、活動性減
退などの感冒様症状をきたす。殊に、患畜がネコ免疫不
全ウイルス(以下、「FIV」と略記することがあ
る。)に感染していると、これら諸症状が一段と顕著に
なり、急速に衰弱する。現在、ネコの呼吸器疾患も含め
て、ネコのウイルス疾患にはこれといった治療法が無
く、呼吸器疾患の場合も、脱水症状を和らげ、体力を回
復させるために補液による栄養療法を施したり、複合感
染や二次感染をしないように抗生物質を投与したり、或
は、単に粘性分泌物を取り除いてやるだけといったよう
な、専ら対症療法的な治療しか行なわれていないのが実
状である。
Cats handled in veterinary hospitals suffer from various infectious diseases, especially respiratory diseases of cats, so-called "cat colds", except those requiring surgical treatment due to trauma or fracture. There are many cases of being brought in. The main cause of a cat cold is thought to be the respiratory tract infection virus, and when the cat is infected, it often causes coughing, runny nose, salivation, fever, upper respiratory tract inflammation, pneumonia, stomatitis, glossitis, conjunctivitis, granulitis, It causes common cold-like symptoms such as tongue ulcer, nasal end ulcer, systemic skin ulcer, turbinate ulcer, diarrhea, vomiting, decreased appetite, decreased activity. In particular, when the sick animal is infected with the feline immunodeficiency virus (hereinafter sometimes abbreviated as "FIV"), these various symptoms become more prominent and rapidly debilitate. At present, there is no such cure for feline viral diseases, including feline respiratory diseases, and even in the case of respiratory diseases, nutritional therapy with fluid replacement is applied to relieve dehydration and restore physical strength, The actual situation is that only symptomatic treatment is performed, such as administration of antibiotics to prevent complex infections or secondary infections, or simply removal of viscous secretions.

【0004】最近、数百万国際単位程度の遺伝子組換型
ネコインターフェロンを静脈内投与してネコの呼吸器疾
患を治療する試みが為され、ある程度の有効性が認めら
れたことが、内野富弥等、『小動物臨床』、第11巻、
第6号、第11〜25頁(1992年)によって報告さ
れた。しかしながら、この方法を効果的に実施しようと
すると、患畜に大量のネコインターフェロンを投与しな
ければならず、飼主の経済的負担が甚だ大きくなる。す
なわち、遺伝子組換型であっても、インターフェロンを
始めとする生理活性ポリペプチドは一般に非常に高価な
のが現状であり、大量のネコインターフェロンを長期連
用するとなると、飼主の経済的負担が大きくなるのは避
けられない。また、一般に、ネコは神経質で警戒心が強
く、取扱いが難しいことから、実際に治療を担当する獣
医師の立場からも、静脈以外に投与して著効の得られる
方法が望ましい。
Recently, an attempt was made to treat respiratory diseases in cats by intravenously administering recombinant feline interferon in the order of several million international units, and it was confirmed that the efficacy was to some extent. Tomiya Uchino Etc., "Small Animal Clinic", Volume 11,
No. 6, 11-25 (1992). However, in order to effectively carry out this method, a large amount of feline interferon must be administered to the sick animal, which greatly increases the financial burden on the owner. That is, even if it is a genetically engineered type, bioactive polypeptides such as interferon are generally very expensive at present, and if a large amount of feline interferon is used for a long period of time, the economical burden on the owner increases. Is inevitable. Further, in general, cats are nervous, vigilant, and difficult to handle. Therefore, from the standpoint of the veterinarian who is actually in charge of treatment, it is preferable to administer a method other than intravenous to obtain a marked effect.

【0005】このようなことから、ネコの呼吸器疾患を
簡便且つ効果的に治療でき、飼主の経済的負担も少ない
方法の開発が希求されている。
Therefore, there is a demand for the development of a method capable of treating respiratory diseases in cats simply and effectively and with less economical burden on the owner.

【0006】[0006]

【発明により解決すべき課題】このような状況に鑑み、
この発明の目的とするところは、静脈以外の経路より投
与しても著効を示し、治療担当者の労力・負担や飼主の
経済的負担が少なくて済むネコの呼吸器疾患治療剤を提
供することにある。
SUMMARY OF THE INVENTION In view of such a situation,
The object of the present invention is to provide a therapeutic agent for respiratory diseases in cats, which shows remarkable effects even when administered by a route other than intravenous, and which requires less labor and burden on the person in charge of treatment and economical burden on the owner. Especially.

【0007】[0007]

【課題を解決するための手段】このような課題を解決す
べく、本発明者等が鋭意研究したところ、HuIFN
は、小用量でネコの呼吸器疾患に伴なう咳、鼻水、流
涎、発熱、上部気道炎、肺炎、口内炎、舌炎、結膜炎、
顆粒性腺炎、舌部潰瘍、鼻端部潰瘍、全身性皮膚潰瘍、
鼻甲介部潰瘍、下痢、嘔吐、食欲減退、活動性減退など
の一般臨床症状の改善に著効を発揮することを見出し
た。しかも、その投与経路は静脈内投与に限定されず、
静脈以外の経路より非経口的に投与したり、経口的に投
与することもできる。
[Means for Solving the Problems] In order to solve such a problem, the present inventors have conducted diligent research and found that HuIFN
Cough, runny nose, salivation, fever, upper respiratory tract inflammation, pneumonia, stomatitis, glossitis, conjunctivitis associated with respiratory disease in cats in small doses.
Granulitis, tongue ulcer, nose end ulcer, systemic skin ulcer,
It was found to be highly effective in improving general clinical symptoms such as turbinate ulcer, diarrhea, vomiting, loss of appetite and loss of activity. Moreover, the administration route is not limited to intravenous administration,
It can also be administered parenterally or orally by a route other than intravenous.

【0008】すなわち、この発明は、HuIFNを有効
成分とするネコの呼吸器疾患治療剤を要旨とするもので
ある。
[0008] That is, the gist of the present invention is a therapeutic agent for respiratory diseases in cats containing HuIFN as an active ingredient.

【0009】インターフェロンは、もともと抗ウイルス
作用のある物質として見出されたものではあるが、種特
異性が高く、ある動物を治療するには、同じ種の動物に
由来するインターフェロンでなければ効果が無いと言わ
れてきた。したがって、ヒト由来のインターフェロンが
ネコの呼吸器疾患の治療に効果のあること自体、全く意
外なことであった。
Although interferon was originally found as a substance having an antiviral effect, it is highly species-specific, and in order to treat a certain animal, it is effective only if the interferon is derived from an animal of the same species. It has been said that there is no. Therefore, it was completely unexpected that human-derived interferon is effective in treating respiratory diseases in cats.

【0010】[0010]

【発明の作用】この発明の治療剤は、呼吸器疾患に罹患
したネコに投与すると、有効成分たるHuIFNが効果
的に作用し、ネコの呼吸器疾患に伴なう咳、鼻水、流
涎、発熱、上部気道炎、肺炎、口内炎、舌炎、結膜炎、
顆粒性腺炎、舌部潰瘍、鼻端部潰瘍、全身性皮膚潰瘍、
鼻甲介部潰瘍、下痢、嘔吐、食欲減退、活動性減退など
の一般臨床症状を改善する。
When the therapeutic agent of the present invention is administered to a cat suffering from a respiratory disease, HuIFN, which is an active ingredient, acts effectively, resulting in cough, runny nose, salivation and fever associated with the respiratory disease of a cat. , Upper respiratory tract inflammation, pneumonia, stomatitis, glossitis, conjunctivitis,
Granulitis, tongue ulcer, nose end ulcer, systemic skin ulcer,
Improve general clinical symptoms such as turbinate ulcer, diarrhea, vomiting, decreased appetite, decreased activity.

【0011】HuIFNは、ネコの呼吸器疾患に対する
治療効果が高く、通常、ネコ体重kg当たり約0.00
5乃至5,000国際単位と極めて小用量で事足りる。
HuIFN has a high therapeutic effect on respiratory diseases in cats, and is usually about 0.00 per kg of cat body weight.
Very small doses of 5 to 5,000 international units are sufficient.

【0012】HuIFNは、静脈以外の経路より非経口
投与しても、経口投与しても、ネコの呼吸器疾患の治療
に著効を発揮する。
HuIFN is remarkably effective in the treatment of respiratory diseases in cats either parenterally or orally by a route other than intravenous.

【0013】以下、実施例などにより、この発明を詳細
に説明する。
The present invention will be described in detail below with reference to examples.

【0014】この発明でいうネコとは、いわゆるネコ科
ネコ属に属する動物であって、ネコの呼吸器疾患の主因
であるネコヘルペスウイルスやネコカリシウイルスなど
の気道感染ウイルスに感受性を有し、これに感染する
か、さらに、FIV、マイコプラズマ、細菌、寄生虫な
どに複合乃至二次感染して、咳、鼻水、流涎、発熱、上
部気道炎、肺炎、口内炎、舌炎、結膜炎、顆粒性腺炎、
舌部潰瘍、鼻端部潰瘍、全身性皮膚潰瘍、鼻甲介部潰
瘍、下痢、嘔吐、食欲減退、活動性減退から選ばれる二
種以上の一般臨床症状を示す動物全般を意味し、通常、
カイネコ全般をその治療対象とするものである。
The cat referred to in the present invention is an animal belonging to the so-called feline genus of cats, and is susceptible to respiratory tract infection viruses such as feline herpes virus and feline calicivirus, which are the main causes of respiratory diseases in cats, Infected with this, or further complex or secondary infection with FIV, mycoplasma, bacteria, parasites, etc., cough, runny nose, salivation, fever, upper respiratory tract inflammation, pneumonia, stomatitis, glossitis, conjunctivitis, granulitis. ,
Tongue ulcer, nose end ulcer, systemic skin ulcer, turbinate ulcer, diarrhea, vomiting, decreased appetite, general animal showing two or more general clinical symptoms selected from decreased activity, usually,
It is intended to treat all the cats.

【0015】この発明によるネコの呼吸器疾患治療剤
は、ヒト由来の細胞か、ヒト由来の細胞から採取したH
uIFN関連遺伝子を導入した微生物若しくは動物細胞
が産生するインターフェロンを有効成分とするものであ
る。今日、HuIFNは、その抗原性の違いに基づき、
主としてHuIFN−α、HuIFN−β、HuIFN
−γなる三種類の型に分類されている。ネコの呼吸器疾
患に対する治療効果においてやや違いはあるものの、何
れもこの発明で使用することができる。その際、ただ一
種の型のHuIFNを使用してもよいし、型の違う二種
以上のHuIFNを組合せて使用してもよい。何れのH
uIFNの場合でも、比活性ができるだけ高いものを使
用するのが望ましく、経口投与には、比活性が約105
国際単位/mg蛋白質以上の部分精製品及び精製品が、
また、非経口投与には、約107国際単位/mg蛋白質
以上の精製品が望ましい。
The therapeutic agent for feline respiratory diseases according to the present invention is a human-derived cell or H collected from a human-derived cell.
The active ingredient is interferon produced by a microorganism or animal cell into which a uIFN-related gene has been introduced. Today, HuIFN is based on its difference in antigenicity,
Mainly HuIFN-α, HuIFN-β, HuIFN
It is classified into three types called γ. Although there are some differences in the therapeutic effects on respiratory diseases in cats, any of them can be used in the present invention. At that time, only one type of HuIFN may be used, or two or more types of HuIFN having different types may be used in combination. Which H
Even in the case of uIFN, it is desirable to use one having as high a specific activity as possible. For oral administration, the specific activity is about 10 5
Partial purified products and purified products with more than international unit / mg protein,
For parenteral administration, a purified product of about 10 7 international units / mg protein or more is desirable.

【0016】本発明者等が試験したところ、これらHu
IFNのうち、HuIFN−α、とりわけ、BALL−
1細胞やナマルバ細胞などのヒトリンパ芽球様細胞株
や、人血から分離した白血球が産生する、いわゆる、
「天然型HuIFN−α」はネコの呼吸器疾患に対する
治療効果が格段に高く、副作用も僅少という特徴があ
る。ことに、BALL−1細胞由来のHuIFN−α
は、サブタイプα2やサブタイプα8などのHuIFN
−αのサブタイプを極めてバランス良く含んでおり、こ
の発明に使用して最上の効果をもたらした。遺伝子組換
型HuIFNは、一般に、治療効果において天然型Hu
IFNに劣り、副作用もやや強い傾向にあった。
The present inventors have tested these Hu
Of IFNs, HuIFN-α, especially BALL-
Produced by human lymphoblastoid cell lines such as 1 cell and Namalwa cell, and white blood cells separated from human blood,
“Natural HuIFN-α” is characterized by a markedly high therapeutic effect on respiratory diseases in cats and few side effects. In particular, HuIFN-α derived from BALL-1 cells
Is a HuIFN such as subtype α2 or subtype α8
It contains a subtype of -α in a very well-balanced manner and has the best effect when used in the present invention. Recombinant HuIFN generally has a therapeutic effect on the native HuIFN.
Inferior to IFN, side effects tended to be rather strong.

【0017】この発明によるネコの呼吸器疾患治療剤
は、HuIFN単独の形態はもとより、HuIFNとそ
れ以外の生理的に許容される、例えば、担体、賦形剤、
希釈剤、免疫助成剤、安定剤、さらには、必要に応じ
て、解熱剤、抗炎症剤、抗菌剤、消化剤、栄養剤、餌料
などとの組成物としての形態を包含する。さらに、この
発明の治療剤は、投薬単位形態の薬剤をも包含し、その
投薬単位形態の薬剤とは、この発明の有効成分たるHu
IFNの、例えば、一日当たりの用量又はその整数倍
(4倍まで)若しくはその約数(1/40まで)に相当
する量を含有し、投与に適する物理的に分離した一体の
剤型にある薬剤を意味する。このような投薬形態の薬剤
としては、注射剤、液剤、ゲル状経口用剤、散剤、顆粒
剤、錠剤、カプセル剤、舌下剤などが挙げられる。
The therapeutic agent for feline respiratory disease according to the present invention is not only in the form of HuIFN alone, but also in the case of HuIFN and other physiologically acceptable ones, such as carrier, excipient,
It includes a diluent, an immunostimulant, a stabilizer, and, if necessary, a composition as a composition with an antipyretic agent, an anti-inflammatory agent, an antibacterial agent, a digestive agent, a nutritional supplement, a feed and the like. Further, the therapeutic agent of the present invention also includes a drug in a dosage unit form, and the drug in the dosage unit form means Hu which is an active ingredient of the present invention.
IFN, for example, in a daily, or an integral multiple (up to 4 times) or equivalent amount (up to 1/40) thereof, in a physically separate, unitary dosage form suitable for administration. Means a drug. Examples of the drug having such a dosage form include injections, liquids, oral gels, powders, granules, tablets, capsules and sublingual agents.

【0018】この発明によるネコの呼吸器疾患治療剤の
用量、用法について説明すると、この発明の治療剤は、
経口的に投与しても非経口的に投与しても、所期の治療
効果が得られる。具体的には、ネコの種類、原因ウイル
スの種類、症状、用量、用法、使用するHuIFNの種
類などに依っても変わるけれども、患畜の症状や様子を
観察しながら、通常、ネコ体重kg当たり約0.005
乃至5,000国際単位/回、望ましくは、約0.5乃
至50国際単位/回、より望ましくは、約1乃至20国
際単位/回のHuIFNを1日1乃至3回若しくは1週
間に1乃至5回、約1日乃至1カ月間投与すればよい。
The dose and usage of the therapeutic agent for feline respiratory diseases according to the present invention will be explained.
The desired therapeutic effect can be obtained by oral or parenteral administration. Specifically, it varies depending on the type of cat, the type of causative virus, the symptoms, the dose, the usage, the type of HuIFN used, etc. 0.005
To 5,000 international units / time, preferably about 0.5 to 50 international units / time, more preferably about 1 to 20 international units / time HuIFN 1 to 3 times a day or 1 to 1 time a week. It may be administered 5 times for about 1 day to 1 month.

【0019】この発明の治療剤を経口投与するには、治
療剤を、例えば、液剤、トローチ剤、散剤、顆粒剤、錠
剤、舌下剤、餌料などの経口投与可能な形態に調製し、
必要に応じて、経口投与器や胃ゾンデなどの適宜投与補
助器具を使いながら、常法にしたがって口腔内、鼻腔
内、食道内若しくは胃内に挿入すればよい。また、非経
口投与するには、この発明による注射剤をネコの皮内、
皮下、筋肉内、静脈内若しくは腹腔内に注射すればよ
い。本発明者等が試験したところ、用量が上記の範囲を
下回ると所期の治療効果が得られ難くなり、逆に、上回
ると、抗体産生や副作用が顕著になったり、治療効果に
比べて飼主の経済的負担が大きくなることがあり、上記
範囲を以て最良とした。
To administer the therapeutic agent of the present invention orally, the therapeutic agent is prepared into an orally administrable form such as a solution, a troche, a powder, a granule, a tablet, a sublingual preparation, and a bait.
If necessary, it may be inserted into the oral cavity, the nasal cavity, the esophagus, or the stomach according to a conventional method while using an appropriate administration aid such as an oral administration device or a gastric tube. Further, for parenteral administration, the injection according to the present invention is applied intradermally to the cat,
It may be injected subcutaneously, intramuscularly, intravenously or intraperitoneally. The inventors of the present invention tested, when the dose is less than the above range, it is difficult to obtain the desired therapeutic effect, and conversely, when the dose is more than the above range, antibody production and side effects become remarkable, or the therapeutic effect is compared to the owner. Since the economic burden of the above may become large, the above range is set as the best value.

【0020】治療効果と投与のし易さという観点から個
々の投与経路を比較すると、経口投与は一般家庭でも容
易に実施できるという利点はあるものの、所定量のHu
IFNを正確に投与するのが難しい欠点がある。これに
より、本来必要とされる以上のHuIFNを投与するこ
とを余儀無くされたり、治療が比較的長期に亙り、飼主
の経済的負担が大きくなることがある。これに対して、
非経口投与の場合は、一般家庭で実施し難いという欠点
はあるものの、患畜に所定量のHuIFNを正確に投与
でき、所期の治療効果を必要最少量のHuIFNで達成
できる利点がある。これにより、患畜を比較的短期間で
完治させることができ、飼主の経済的負担もより少なく
て済む。とりわけ、この発明の治療剤を皮内、皮下若し
くは筋肉内に投与するときには、経口投与や上記以外の
経路より非経口投与する場合に比べてより少量のHuI
FNで事足り、投与がし易く、飼主の経済的負担も僅少
となる。このことは、天然型HuIFN−α、とりわ
け、BALL−1細胞由来のHuIFN−αの場合、特
に顕著であった。
Comparing individual routes of administration from the viewpoint of therapeutic effect and easiness of administration, oral administration has the advantage that it can be easily carried out in general households, but a certain amount of Hu is used.
The drawback is that it is difficult to administer IFN accurately. As a result, it may be necessary to administer more HuIFN than originally required, or the treatment may take a relatively long period of time, increasing the financial burden on the owner. On the contrary,
Although parenteral administration has the drawback that it is difficult to carry out in a general household, it has the advantage that a prescribed amount of HuIFN can be accurately administered to the patient and that the desired therapeutic effect can be achieved with the minimum necessary amount of HuIFN. As a result, the sick animal can be completely cured in a relatively short period of time, and the economic burden on the owner can be reduced. In particular, when the therapeutic agent of the present invention is administered intradermally, subcutaneously or intramuscularly, a smaller amount of HuI is used than oral administration or parenteral administration by a route other than the above.
FN is sufficient, it is easy to administer, and the financial burden on the owner is also minimal. This was particularly remarkable in the case of native HuIFN-α, particularly HuIFN-α derived from BALL-1 cells.

【0021】なお、本明細書を通じて、HuIFNの活
性は、HuIFNがシンドビスウイルスによるFL細胞
の細胞変性を抑制する度合をマイクロタイター法により
測定し、その測定値を世界保健機関によるHuIFNの
国際標準品「Ga23−901−532」に基づき「国
際単位」に換算して表示している。
[0021] Throughout the present specification, the activity of HuIFN is measured by the microtiter method to determine the degree to which HuIFN suppresses the cytopathic modification of FL cells by Sindbis virus, and the measured value is the international standard of HuIFN by the World Health Organization. Based on the product "Ga23-901-532", it is converted into "international units" and displayed.

【0022】以下、2〜3の実施例に基づき、この発明
をより具体的に説明する。
Hereinafter, the present invention will be described more specifically based on a few examples.

【0023】[0023]

【実施例1 乾燥注射剤】特公昭56−54158号公
報に記載された方法に準じ、ハムスター体内で増殖させ
たBALL−1細胞に培養培地中でセンダイウイルスを
作用させてインターフェロンを誘発させた。この培養培
地を遠心分離して得られた上清を濃縮し、濃縮物にフェ
ニルセファロースを用いるアフィニティークロマトグラ
フィーを適用することにより、比活性約106国際単位
/mg蛋白質の部分精製HuIFNを得た。次に、この
部分精製HuIFNを、常法により、モノクローナル抗
HuIFN−α抗体を水不溶性担体に結合させたセルテ
ック社製『NK−2セファロース』を用いるアフィニテ
ィークロマトグラフィーによりさらに精製した後、ネコ
血清アルブミン約0.1mg/mlを含有する燐酸緩衝
液(pH7.0)で平衡化させたゲル濾過クロマトグラ
フィーを適用することにより、比活性約2×108国際
単位/mgの精製HuIFN−αを含有するHuIFN
−α溶液を得た。
Example 1 Dry injection: According to the method described in Japanese Patent Publication No. 56-54158, BALL-1 cells grown in a hamster body were made to act on Sendai virus in a culture medium to induce interferon. The culture medium was centrifuged to obtain a supernatant, which was concentrated, and affinity chromatography using phenyl sepharose was applied to the concentrate to obtain a partially purified HuIFN having a specific activity of about 10 6 international units / mg protein. . Next, this partially purified HuIFN was further purified by affinity chromatography using "NK-2 Sepharose" manufactured by Celtec in which a monoclonal anti-HuIFN-α antibody was bound to a water-insoluble carrier by a conventional method, and then feline serum albumin. By applying gel filtration chromatography equilibrated with phosphate buffer (pH 7.0) containing about 0.1 mg / ml, a specific activity of about 2 × 10 8 international units / mg of purified HuIFN-α is contained. HuIFN
-A solution was obtained.

【0024】このようにして調製した精製HuIFN−
αを約5mg蛋白質/mlにまで膜濃縮し、1%(w/
v)ネコ血清アルブミンと0.01M燐酸緩衝液(pH
7.0)を含有する生理食塩水にHuIFN−α濃度が
15国際単位/mlになるよう希釈し、膜濾過して滅菌
した後、バイアルに1mlずつ無菌的に充填し、凍結乾
燥した。
Purified HuIFN-prepared in this way
Membrane concentration of α to about 5 mg protein / ml, 1% (w /
v) Feline serum albumin and 0.01M phosphate buffer (pH
It was diluted in a physiological saline solution containing 7.0) so that the HuIFN-α concentration would be 15 international units / ml, sterilized by membrane filtration, and then aseptically filled in 1 ml vials and lyophilized.

【0025】本品は、有効成分としてBALL−1細胞
由来の精製HuIFN−αを含有し、賦形剤たる血清ア
ルブミンはネコ由来のものを使用しているので、ネコの
呼吸器疾患治療用注射剤として有用である。
This product contains purified HuIFN-α derived from BALL-1 cells as an active ingredient, and serum albumin as a vehicle is derived from cats. It is useful as an agent.

【0026】[0026]

【実施例2 乾燥注射剤】常法により、人血から分離し
た白血球にセンダイウイルスを作用させて誘発させたH
uIFNをケー・カンテル(K.Cantell)等、
『ザ・ジャーナル・オブ・ジェネラル・バイロロジー
(The Journal of General V
irology)』、第39巻、第541〜543頁
(1978年)に記載された方法に準じて精製し、比活
性約2×106国際単位/mg蛋白質の部分精製HuI
FNを得た。次いで、この部分精製HuIFNを、実施
例1と同様、モノクローナル抗HuIFN−α抗体を用
いる抗体クロマトグラフィーによりさらに精製した後、
局方精製ゼラチン約0.1mg/mlを含有する燐酸緩
衝液(pH7.0)で平衡化させたゲル濾過クロマトグ
ラフィーを適用することにより、比活性約2×108
際単位/mgの精製HuIFN−αを含有するHuIF
N−α溶液を得た。
[Example 2 Dry injection] H produced by causing Sendai virus to act on leukocytes separated from human blood by a conventional method
uIFN, K. Cantel, etc.
"The Journal of General Virology (The Journal of General V
irology) ”, Vol. 39, pp. 541-543 (1978), and purified to a specific activity of about 2 × 10 6 international units / mg protein partially purified HuI.
I got FN. Then, this partially purified HuIFN was further purified by antibody chromatography using a monoclonal anti-HuIFN-α antibody as in Example 1, and
By applying gel filtration chromatography equilibrated with a phosphate buffer (pH 7.0) containing about 0.1 mg / ml of pharmacopoeia, purified HuIFN with a specific activity of about 2 × 10 8 international units / mg. HuIF containing α
An N-α solution was obtained.

【0027】このようにして調製した精製HuIFN−
αを約5mg蛋白質/mlにまで膜濃縮し、1%(w/
v)局方精製ゼラチンと0.01M燐酸緩衝液(pH
7.0)を含有する生理食塩水にHuIFN−α濃度が
20国際単位/mlになるよう希釈し、膜濾過して滅菌
した後、バイアルに1mlずつ無菌的に充填し、凍結乾
燥した。
Purified HuIFN-prepared in this way
Membrane concentration of α to about 5 mg protein / ml, 1% (w /
v) Pharmacopoeial purified gelatin and 0.01M phosphate buffer (pH
It was diluted in a physiological saline solution containing 7.0) so that the HuIFN-α concentration was 20 international units / ml, sterilized by membrane filtration, and then aseptically filled in vials in an amount of 1 ml and freeze-dried.

【0028】有効成分としてヒト白血球由来の精製Hu
IFN−αを含有せしめた本品は、治療効果及び副作用
において実施例1の注射剤よりやや劣るものの、ネコの
呼吸器疾患治療用注射剤として有用である。
Purified Hu derived from human leukocytes as an active ingredient
Although this product containing IFN-α is slightly inferior to the injection of Example 1 in therapeutic effect and side effect, it is useful as an injection for treating respiratory diseases in cats.

【0029】[0029]

【実施例3 乾燥注射剤】実施例1と同様にしてBAL
L−1細胞にセンダイウイルスを作用させて調製した精
製HuIFN−αを、3%(w/v)ネコ血清アルブミ
ンと0.1M燐酸緩衝液(pH7.0)を含有する生理
食塩水にHuIFN−α濃度が20,000国際単位/
mlとなるように希釈し、膜濾過して滅菌した後、バイ
アルに1mlずつ充填し、凍結乾燥した。
Example 3 Dry Injection BAL as in Example 1
Purified HuIFN-α prepared by allowing Sendai virus to act on L-1 cells was added to a physiological saline containing 3% (w / v) feline serum albumin and 0.1 M phosphate buffer (pH 7.0) HuIFN-. α concentration is 20,000 international units /
After diluting to have a volume of 1 ml, sterilizing by filtration through a membrane, 1 ml was filled in each vial and freeze-dried.

【0030】本品は、実施例1の注射剤と同様、有効成
分としてBALL−1細胞由来の精製HuIFN−αを
含有し、賦形剤たる血清アルブミンはネコ由来のものを
使用しているので、ネコの呼吸器疾患治療用注射剤とし
て有用である。
Like the injection of Example 1, this product contains purified HuIFN-α derived from BALL-1 cells as an active ingredient, and the serum albumin used as a vehicle is derived from cats. , Useful as an injection for treating respiratory diseases in cats.

【0031】[0031]

【実施例4 ゲル状経口用剤】蒸留水にウシ血清アルブ
ミンを1%(w/v)溶解し、溶液に実施例1の方法で
調製したBALL−1細胞由来の部分精製HuIFNを
含有する溶液を加え、1g当たりHuIFNを300国
際単位含有するHuIFN溶液を得た。この溶液32.
0重量部に0.5重量部の『ツイーン80』を15.0
重量部のエタノールに溶解して混合し、さらに、その混
合物に0.5重量部のトリエタノールアミンを15.0
重量部のグリセリンに溶解して混合した後、少量のトリ
エタノールアミンを加えて、ml当たりHuIFNを約
100国際単位含む、ほぼ中性のゲル状製剤を得た。
Example 4 Gel Oral Agent A solution containing 1% (w / v) of bovine serum albumin in distilled water and containing the partially purified HuIFN derived from BALL-1 cells prepared by the method of Example 1 in the solution. Was added to obtain a HuIFN solution containing 300 international units of HuIFN per gram. This solution 32.
0.5 parts by weight of “Tween 80” to 0 parts by weight of 15.0
Dissolve and mix in 1 part by weight of ethanol, and further add 15.0 parts by weight of triethanolamine to the mixture.
After dissolving in 1 part by weight of glycerin and mixing, a small amount of triethanolamine was added to obtain a nearly neutral gel-like preparation containing about 100 international units of HuIFN per ml.

【0032】有効成分としてBALL−1細胞由来のH
uIFNを含有する本品は、適度の口腔内滞留時間を有
し、患畜に飲ませ易い呼吸器疾患治療用ゲル状経口用剤
である。
H derived from BALL-1 cells as an active ingredient
The product containing uIFN is a gel-type oral preparation for treating respiratory diseases, which has an appropriate residence time in the oral cavity and is easily drinkable by patients.

【0033】[0033]

【実施例5 散剤】株式会社林原が製造する高純度無水
結晶マルトース製品『ファイントース』100重量部に
実施例2の方法で調製したヒト白血球由来の部分精製H
uIFN(約106国際単位/ml)2重量部を均一に
噴霧し、真空乾燥し、粉砕した後、篩にかけて粒度10
0乃至500ミクロンの粉状物を得た。粉状物にさらに
適当量の『ファイントース』を均一に混合し、1g当た
りHuIFNを約100国際単位含む散剤を得た。
[Example 5 Powder] Partially purified H derived from human leukocytes prepared by the method of Example 2 in 100 parts by weight of a high-purity anhydrous crystalline maltose product "Finetose" manufactured by Hayashibara Co., Ltd.
2 parts by weight of uIFN (about 10 6 international units / ml) was uniformly sprayed, vacuum-dried, crushed, and sieved to give a particle size of 10
A powder of 0 to 500 microns was obtained. The powdery substance was further uniformly mixed with an appropriate amount of "FINETOSE" to obtain a powder containing about 100 international units of HuIFN per gram.

【0034】本品は適度の口腔内滞留時間と優れた保存
安定性を有し、ネコの呼吸器疾患治療用散剤として有用
である。本品は適度の甘味を有し、ネコの口腔内に投与
して刺激少なく、患畜に飲ませ易い散剤である。
This product has an appropriate retention time in the oral cavity and excellent storage stability, and is useful as a powder for treating respiratory diseases in cats. This product has a moderate sweetness, is a powder that can be administered to the sick of animals and administered to the oral cavity of cats without causing irritation.

【0035】[0035]

【実施例6 顆粒剤】株式会社林原が製造する高純度無
水結晶マルトース製品『ファイントース』100重量部
に実施例1の方法で調製したBALL−細胞由来の部分
精製HuIFNを含有する水溶液(約30,000国際
単位/ml)15重量部を均一に混ぜたの後、打錠機に
かけて顆粒剤を得た。
Example 6 Granules An aqueous solution containing 100 parts by weight of high-purity anhydrous crystalline maltose product “Finetose” manufactured by Hayashibara Co., Ltd. and partially purified HuIFN derived from BALL-cells prepared by the method of Example 1 (about 30 After uniformly mixing 15 parts by weight (1,000 international units / ml), the mixture was tableted to obtain granules.

【0036】本品は、1g当たりHuIFNを約4,4
00国際単位含み、優れた保存安定性を有し、ネコの呼
吸器疾患治療用散剤として有用である。また、本品は適
度の甘味を有し、ネコの口腔内に投与して刺激少なく、
患畜に飲ませ易い顆粒剤である。
This product contains about 4 and 4 HuIFN per gram.
It contains 00 international units, has excellent storage stability, and is useful as a powder for treating respiratory diseases in cats. In addition, this product has a moderate sweetness and is administered to the cat's oral cavity with less irritation,
It is a granule that can be easily given to patients.

【0037】次に、実施例の治療剤を使用して行った臨
床試験について説明する。
Next, a clinical test conducted using the therapeutic agent of the example will be described.

【0038】[0038]

【実験例1 臨床試験】咳、鼻水、流涎、発熱、上部気
道炎、肺炎、口内炎、舌炎、結膜炎、顆粒性腺炎、舌部
潰瘍、鼻端部潰瘍、全身性皮膚潰瘍、鼻甲介部潰瘍、下
痢、嘔吐、食欲減退、活動性減退などを主徴として動物
病院に持ち込まれ、診断の結果、呼吸器疾患と判定され
たカイネコ52匹につき、実際に実施例1の乾燥注射剤
を投与し、その経過を観察することにより、この発明に
よる治療剤の効果と副作用を評価した。
[Experimental Example 1 Clinical study] Cough, runny nose, salivation, fever, upper respiratory tract inflammation, pneumonia, stomatitis, glossitis, conjunctivitis, granulitis, tongue ulcer, nose tip ulcer, systemic skin ulcer, nasal concha ulcer , The diarrhea, vomiting, decreased appetite, decreased activity, etc. were brought to the veterinary hospital, and the dry injection of Example 1 was actually administered to 52 Kanekos judged to have respiratory disease as a result of the diagnosis. The effects and side effects of the therapeutic agent according to the present invention were evaluated by observing the progress thereof.

【0039】すなわち、初診時の一般臨床所見から呼吸
器疾患と診断され、且つ、ウイルス検査の結果、FIV
抗体陽性と判定された1乃至6歳と推定される雄ネコ3
3匹と雌ネコ19匹を対象とし、その頸部皮下に体重k
g当たり約1乃至20国際単位/回の用量で実施例1の
乾燥注射剤を毎日1回、1週間に亙って注射投与した。
投与開始直後より経過を注意深く観察し、用量ととも
に、全身状態、脱水状態、食欲 、飲水欲、活動性、鼻
水、咳、下痢、流涎、結膜炎、口内炎、鼻端部潰瘍、呼
吸様式、嘔吐など計14項目の一般臨床所見を記録し
た。なお、ウイルス検査の結果、患畜の殆どは、ネコヘ
ルペスウイルスおよび/またはネコカリシウイルスとの
複合感染が疑われた。
That is, the respiratory disease was diagnosed from the general clinical findings at the time of the first medical examination, and the result of the virus test was FIV.
Male cats presumed to be 1 to 6 years old with antibody positive test
Targeting 3 and 19 female cats, the weight k
The dry injection of Example 1 was administered by injection once a day for 1 week at a dose of about 1 to 20 international units / g / g.
Careful observation of the course immediately after the start of administration, together with the dose, showed general condition, dehydration, appetite, water desire, activity, runny nose, cough, diarrhea, salivation, conjunctivitis, stomatitis, nasal end ulcer, respiratory mode, vomiting, etc. Fourteen general clinical findings were recorded. As a result of the virus test, most of the affected animals were suspected to have a combined infection with feline herpesvirus and / or feline calicivirus.

【0040】臨床実験は主として獣医師が行ない、患畜
の様子や症状、副作用などを観察しながら、インターフ
ェロンの用量や投与回数を調節した。そして、投与を終
了した時点で結果を取り纒め、次の判定規準に基づいて
この発明による治療剤の有効性を判定した。すなわち、
5日以内にすべての症状が正常に復帰したものは「著
効」とする、口内炎が初診時よりは改善し、且つ、他の
3項目以上の症状が改善するか、口内炎が発症せず、他
の5項目が改善したものは「有効」とする、口内炎は改
善しないものの、他の4項目以上が改善したものは「や
や有効」とする、何れの症状も改善しなかったものは
「無効」とする、そして、症状が悪化したものは「悪
化」とするというものである。
Clinical experiments were mainly conducted by a veterinarian, and the dose of interferon and the number of administrations were adjusted while observing the appearance, symptoms, side effects, etc. of the affected animals. Then, when the administration was completed, the results were compiled and the effectiveness of the therapeutic agent according to the present invention was determined based on the following criteria. That is,
If all symptoms return to normal within 5 days, it is said to be “effective”. Stomatitis is improved from the initial diagnosis, and other three or more symptoms are improved, or stomatitis does not develop, If the other 5 items are improved, the result is “effective”. Stomatitis is not improved, but if the other 4 items or more are improved, the result is “slightly effective”. And, if the symptom worsens, it is said to be "worse".

【0041】臨床実験の結果、何れの臨床例において
も、投与開始直後から3日以内に咳、鼻水、流涎及び下
痢が停止し、体温も正常値の37℃台に回復した。そし
て、投与開始から1週間以内に、上部気道炎、口内炎、
結膜炎及び鼻端部潰瘍が顕著に改善乃至修復し、食欲や
活動性が向上した。上記の判定規準に基づいて判定した
ところ、全52臨床例のうち、「著効」が28例、「有
効」が15例、「やや有効」が5例、「無効」が4例、
「悪化」が0例と、全52例のうち「著効」、「有効」
又は「やや有効」と判定される臨床例が約92%にも達
した。しかも、投与期間中、特段の副作用は全く認めら
れず、この発明による治療剤がネコの呼吸器疾患の治療
に極めて効果的且つ安全であることを裏付けていた。な
お、一部の患畜については、完治後も血液検査を継続し
たところ、HuIFN−αに起因するとおもわれる抗体
産生は全く検出されなかった。このことは、この発明に
よる治療剤が、ネコの呼吸器疾患を治療する目的で、同
一のネコに反復投与しても安全なことを示唆している。
As a result of clinical experiments, in all clinical cases, cough, runny nose, salivation and diarrhea stopped within 3 days immediately after the start of administration, and the body temperature recovered to the normal range of 37 ° C. Within 1 week after the start of administration, upper respiratory tract inflammation, stomatitis,
Conjunctivitis and nasal ulcer were significantly improved or repaired, and appetite and activity were improved. Judgment based on the above criteria, out of a total of 52 clinical cases, 28 cases were "excellent", 15 cases were "effective", 5 cases were "slightly effective", 4 cases were "ineffective",
"Exacerbation" was 0, and "outstanding" and "effective" out of 52 cases
Or, the clinical cases judged to be “slightly effective” reached about 92%. Moreover, no particular side effect was observed during the administration period, demonstrating that the therapeutic agent according to the present invention is extremely effective and safe for the treatment of respiratory diseases in cats. In addition, when blood tests were continued for some of the sick animals even after being completely cured, no antibody production, which was considered to be caused by HuIFN-α, was detected. This suggests that the therapeutic agent according to the present invention is safe for repeated administration to the same cat for the purpose of treating respiratory diseases in cats.

【0042】上記知見に基づき、実施例2、4および5
の実施態様についても同様の臨床実験をしたところ、非
経口投与で約70%以上、経口投与でも約60%以上
と、極めて優秀な治療成績が得られた。非経口投与に比
べると、経口投与の有効率がやや低いが、普通一般の薬
剤より遥かに高いものである。なお、非経口投与は、皮
内、皮下、筋肉内、静脈内若しくは腹腔内への注射に依
ったが、用量が僅少なことから、注射針を挿入する時間
が短かくて済み、殆どの患畜が暴れだすことなく、ほぼ
一回の挿入で投与を完了できた。
Based on the above findings, Examples 2, 4 and 5
When the same clinical experiment was carried out for the above embodiment, extremely excellent therapeutic results were obtained, that is, about 70% or more by parenteral administration and about 60% or more by oral administration. The efficacy rate of oral administration is slightly lower than that of parenteral administration, but much higher than that of ordinary drugs. Parenteral administration relied on intradermal, subcutaneous, intramuscular, intravenous or intraperitoneal injections, but the dose was so small that it took only a short time to insert the injection needle, and The administration could be completed with almost one insertion without the rampage.

【0043】なお、実施例1、2、4および5の実施態
様で使用する部分精製HuIFN及び精製HuIFN−
αにつき、健常ネコを対象に急性毒性試験したところ、
何れもネコに対する毒性の極めて低いことが判明した。
The partially purified HuIFN and the purified HuIFN- used in the embodiments of Examples 1, 2, 4 and 5.
When α was tested for acute toxicity in healthy cats,
All were found to have extremely low toxicity to cats.

【0044】[0044]

【実験例2 臨床試験】実験例1で使用したカイネコと
同様の症状を呈し、呼吸器疾患と診断されたカイネコ4
0匹について実施例3の乾燥注射剤を投与し、投与後の
経過を観察することにより、その効果と副作用を評価し
た。
[Experimental example 2 clinical test] Kaneko 4 showing the same symptoms as the one used in Experimental example 1 and diagnosed as a respiratory disease.
The effect and side effects were evaluated by administering the dry injection of Example 3 to 0 animals and observing the progress after administration.

【0045】すなわち、初診時の一般臨床所見から呼吸
器疾患と診断され、且つ、ウイルス検査の結果、FIV
抗体陽性と判定された1乃至6歳と推定される雄ネコ1
9匹と雌ネコ21匹を対象とし、その背部皮下に体重k
g当たり約500乃至5,000国際単位/回の用量で
実施例3の乾燥注射剤を毎日1回、1週間に亙って注射
投与した。投与開始直後より経過を注意深く観察し、用
量とともに、実施例1と同様、14項目の一般臨床所見
を記録した。
That is, respiratory disease was diagnosed based on the general clinical findings at the first examination, and the result of the virus test showed that
Male cat 1 presumed to be 1 to 6 years old with antibody positive
Nine and 21 female cats were weighed subcutaneously on their backs.
The dried injection of Example 3 was administered by injection once a day for 1 week at a dose of about 500 to 5,000 international units / g / g. The course was carefully observed immediately after the start of administration, and as with Example 1, 14 general clinical findings were recorded together with the dose.

【0046】臨床実験は主として獣医師が行ない、患畜
の様子や症状、副作用などを観察しながら、インターフ
ェロンの用量や投与回数を調節した。そして、投与を終
了した時点で結果を取り纒め、実験例1と同じ判定規準
に基づいて本品の有効性を判定した。
Clinical experiments were mainly conducted by a veterinarian, and the dose of interferon and the frequency of administration were adjusted while observing the appearance, symptoms, side effects, etc. of the sick animal. Then, when the administration was completed, the results were compiled and the effectiveness of this product was determined based on the same criteria as in Experimental Example 1.

【0047】臨床試験の結果、何れの臨床例において
も、投与開始直後から臨床症状の改善が認められ、3日
以内に咳、鼻水、流涎及び下痢が停止し、体温も正常値
の37℃台に回復した。そして、投与開始から1週間以
内に、上部気道炎、口内炎、結膜炎及び鼻端部潰瘍が顕
著に改善乃至修復し、食欲や活動性が向上した。
As a result of the clinical test, in all clinical cases, improvement of clinical symptoms was observed immediately after the initiation of administration, cough, runny nose, salivation and diarrhea were stopped within 3 days, and the body temperature was in the normal range of 37 ° C. Recovered. Within 1 week after the start of administration, upper respiratory tract inflammation, stomatitis, conjunctivitis, and nasal ulcer were markedly improved or repaired, and appetite and activity were improved.

【0048】上記の判定規準に基づいて判定したとこ
ろ、全40臨床例のうち、「著効」が25例、「有効」
が11例、「やや有効」が2例、「無効」が2例、「悪
化」が0例と、全40例のうち「著効」、「有効」又は
「やや有効」と判定される臨床例が95%にも達した。
しかも、投与期間中、特段の副作用は全く認められず、
この発明による治療剤がネコの呼吸器疾患の治療に極め
て効果的且つ安全であることを裏付けていた。なお、一
部の患畜については、完治後も血液検査を継続したとこ
ろ、HuIFN−αに起因するとおもわれる抗体産生は
全く検出されなかった。このことは、この発明による治
療剤が、ネコの呼吸器疾患を治療する目的で、同一のネ
コに体重kg当たり約500乃至5,000国際単位を
反復投与しても安全なことを示唆している。
Judgment was carried out based on the above-mentioned criteria, and out of all 40 clinical cases, "serious effect" was 25 and "effective".
11 cases, “slightly effective” in 2 cases, “ineffective” in 2 cases, and “exacerbation” in 0 cases, clinically judged to be “excellent”, “effective” or “slightly effective” out of all 40 cases The number of cases reached 95%.
Moreover, no particular side effects were observed during the administration period,
It has been proved that the therapeutic agent according to the present invention is extremely effective and safe for the treatment of respiratory diseases in cats. In addition, when blood tests were continued for some of the sick animals even after being completely cured, no antibody production, which was considered to be caused by HuIFN-α, was detected. This suggests that the therapeutic agent according to the present invention is safe for repeated administration of about 500 to 5,000 international units per kg body weight to the same cat for the purpose of treating respiratory diseases in cats. There is.

【0049】上記知見に基づき、実施例6の実施態様に
ついても同様の臨床実験をしたところ、経口投与で約7
5%以上の極めて優秀な治療成績が得られた。非経口投
与に比べると、経口投与の有効率がやや低いが、普通一
般の薬剤より遥かに高いものである。
Based on the above findings, the same clinical experiment was conducted for the embodiment of Example 6, and it was found that about 7
An extremely excellent treatment result of 5% or more was obtained. The efficacy rate of oral administration is slightly lower than that of parenteral administration, but much higher than that of ordinary drugs.

【0050】なお、実施例3及び6の実施態様で使用す
る部分精製HuIFN及び精製HuIFN−αにつき、
健常ネコを対象に急性毒性試験したところ、何れもネコ
に対する毒性の極めて低いことが判明した。
Regarding the partially purified HuIFN and the purified HuIFN-α used in the embodiments of Examples 3 and 6,
An acute toxicity test in healthy cats revealed that the toxicity to cats was extremely low.

【0051】[0051]

【急性毒性試験】0.01M燐酸緩衝液(pH7.0)
を含む生理食塩水に、ネコ血清アルブミンと実施例1又
は実施例2の方法で調製したBALL−1細胞又はヒト
白血球由来の部分精製HuIFN又は精製HuIFN−
αとを、この順序で、それぞれの最終濃度が0.1%
(w/v)及び1×106国際単位/mlになるよう溶
解した。かくして得られる4種類の溶液を生後1乃至2
年と推定される健常な雑種ネコ5匹/群からなる4群に
対して、体重kg当たり、この発明における最大投与量
の2万倍に当たる1×106国際単位のHuIFNに相
当する量の生理食塩水を皮下若しくは経口投与し、投与
後の経過を観察した。対照群には、HuIFNを溶解し
なかったこと以外、前記と同様に調製した同量の生理食
塩水を同じ経路で投与した。
[Acute toxicity test] 0.01M phosphate buffer (pH 7.0)
Partially purified HuIFN or purified HuIFN-derived from BALL-1 cells or human leukocytes prepared by the method of Example 1 or Example 2 in physiological saline containing
α and, in this order, the final concentration of each is 0.1%
(W / v) and 1 × 10 6 international units / ml were dissolved. The four kinds of solutions thus obtained are 1 to 2 after birth.
For 4 groups of 5 healthy hybrid cats / group estimated to be 1 year, an amount of physiology equivalent to 1 × 10 6 international units of HuIFN, which is 20,000 times the maximum dose of the present invention, per kg body weight. Saline was subcutaneously or orally administered, and the course after administration was observed. To the control group, the same amount of physiological saline prepared in the same manner as above was administered by the same route except that HuIFN was not dissolved.

【0052】その結果、いずれのHuIFNでも試験群
と対照群とで有意差は認められず、投与後における死亡
例や、投与前後における一般状態、体重、摂餌量にも特
段の変化は認められなかった。このことは、HuIFN
が、ネコに投与して、極めて毒性の低いことを示唆して
いる。
As a result, no significant difference was observed between the test group and the control group in any of the HuIFNs, and there were no particular changes in post-administration deaths, general conditions before and after administration, body weight, and food consumption. There wasn't. This means that HuIFN
However, it has been suggested that it is extremely less toxic when administered to cats.

【0053】[0053]

【発明の効果】叙上のとおり、本発明によるネコの呼吸
器疾患治療剤は、HuIFNを有効成分としているの
で、ネコの呼吸器疾患に伴なう咳、鼻水、流涎、発熱、
上部気道炎、肺炎、口内炎、舌炎、結膜炎、顆粒性腺
炎、舌部潰瘍、鼻端部潰瘍、全身性皮膚潰瘍、鼻甲介部
潰瘍、下痢、嘔吐、食欲減退、活動性減退などの一般臨
床症状の改善に著効を発揮する。
INDUSTRIAL APPLICABILITY As described above, since the therapeutic agent for feline respiratory diseases according to the present invention contains HuIFN as an active ingredient, it causes cough, runny nose, salivation, fever,
Upper respiratory tract inflammation, pneumonia, stomatitis, glossitis, conjunctivitis, granular adenitis, tongue ulcer, nose ulcer, systemic skin ulcer, turbinate ulcer, diarrhea, vomiting, decreased appetite, decreased activity, etc. It is extremely effective in improving symptoms.

【0054】しかも、本発明の治療剤が有効成分として
含有するHuIFNは、患畜に大量投与しても安全であ
る上、小用量でも著効を発揮するので、小用量投与の場
合は、飼主の経済的負担を大幅に低減する。同じ理由に
より、本発明の治療剤によるときには、インターフェロ
ンを必ずしも患畜の静脈内に投与する必要が無くなり、
経口投与や、皮内、皮下、筋肉内などの静脈以外の経路
より非経口的に投与することによっても、所期の効果が
得られる。これにより、神経質で警戒心が強いネコに所
定量のHuIFNを確実且つ容易に投与できることとな
り、獣医師等の治療担当者の労力・負担も大幅に低減す
る。
Furthermore, HuIFN, which the therapeutic agent of the present invention contains as an active ingredient, is safe even when administered to a large amount of sick animals, and exerts a marked effect even in a small dose. Greatly reduce the financial burden. For the same reason, when using the therapeutic agent of the present invention, it is not necessary to administer interferon intravenously to a patient,
The intended effect can also be obtained by oral administration or parenterally by a route other than intravenous such as intracutaneous, subcutaneous and intramuscular. As a result, a predetermined amount of HuIFN can be reliably and easily administered to a nervous and vigilant cat, and the labor and burden of a veterinarian or other person in charge of treatment can be significantly reduced.

【0055】以上の諸効果は、有効成分として天然型H
uIFN−α、とりわけ、BALL−1細胞由来のHu
IFN−αを配合使用することによって、いよいよ顕著
となる。
The above-mentioned effects are obtained by using natural type H as an active ingredient.
uIFN-α, especially Hu from BALL-1 cells
By using IFN-α in combination, it becomes more remarkable.

【0056】この発明は、斯くも顕著な作用効果を奏す
る発明であって、斯界に貢献すること誠に多大な発明で
ある。
The present invention is an invention having such remarkable effects and is a great invention that contributes to the field.

───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 FI 技術表示箇所 A61K 9/14 X 9455−4C ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Office reference number FI technical display area A61K 9/14 X 9455-4C

Claims (11)

【特許請求の範囲】[Claims] 【請求項1】 ヒトインターフェロンを有効成分とする
ネコの呼吸器疾患治療剤。
1. A therapeutic agent for respiratory diseases in cats, which comprises human interferon as an active ingredient.
【請求項2】 ヒトインターフェロンがヒトインターフ
ェロン−αである請求項1に記載のネコの呼吸器疾患治
療剤。
2. The therapeutic agent for respiratory diseases in cats according to claim 1, wherein the human interferon is human interferon-α.
【請求項3】 ヒトインターフェロンが天然型ヒトイン
ターフェロンである請求項1又は2に記載のネコの呼吸
器疾患治療剤。
3. The therapeutic agent for respiratory diseases in cats according to claim 1 or 2, wherein the human interferon is a natural human interferon.
【請求項4】 ヒトインターフェロンがヒトリンパ芽球
様細胞株の産生する天然型ヒトインターフェロン−αで
ある請求項1、2又は3に記載のネコの呼吸器疾患治療
剤。
4. The therapeutic agent for respiratory diseases in cats according to claim 1, 2 or 3, wherein the human interferon is natural human interferon-α produced by a human lymphoblastoid cell line.
【請求項5】 ヒトインターフェロンが、投与されるネ
コの体重1kg当たり約0.005乃至5,000国際
単位含有せしめられている請求項1、2、3又は4に記
載のネコの呼吸器疾患治療剤。
5. The treatment of respiratory diseases in cats according to claim 1, wherein human interferon is contained in an amount of about 0.005 to 5,000 international units per kg body weight of the cat to which it is administered. Agent.
【請求項6】 投薬形態が経口投与形態または非経口投
与形態である請求項1、2、3、4又は5に記載のネコ
の呼吸器疾患治療剤。
6. The therapeutic agent for respiratory diseases in cats according to claim 1, 2, 3, 4, or 5, wherein the dosage form is an oral dosage form or a parenteral dosage form.
【請求項7】 ヒトインターフェロンをネコ体重1kg
当たり約0.005乃至5,000国際単位/回投与す
ることを特徴とするネコの呼吸器疾患治療方法。
7. A human body weight of 1 kg of human interferon
A method for treating a respiratory disease in a cat, which comprises administering about 0.005 to 5,000 international units per administration.
【請求項8】 ヒトインターフェロンがヒトインターフ
ェロン−αである請求項7に記載のネコの呼吸器疾患治
療方法。
8. The method for treating respiratory diseases in cats according to claim 7, wherein the human interferon is human interferon-α.
【請求項9】 ヒトインターフェロンが天然型ヒトイン
ターフェロンである請求項7又は8に記載のネコの呼吸
器疾患治療方法。
9. The method for treating a respiratory disease in a cat according to claim 7, wherein the human interferon is a natural human interferon.
【請求項10】 ヒトインターフェロンがヒトリンパ芽
球様細胞株の産生する天然型ヒトインターフェロン−α
である請求項7、8又は9に記載のネコの呼吸器疾患治
療方法。
10. Human interferon-natural human interferon-α produced by a human lymphoblastoid cell line.
10. The method for treating a respiratory disease of a cat according to claim 7, 8 or 9.
【請求項11】 投薬形態が経口投与形態または非経口
投与形態である請求項7、8、9、又は10に記載のネ
コの呼吸器疾患治療方法。
11. The method for treating respiratory diseases in cats according to claim 7, 8, 9 or 10, wherein the dosage form is an oral dosage form or a parenteral dosage form.
JP09554294A 1993-04-09 1994-04-09 Cat respiratory remedy and therapeutic method using the same Expired - Fee Related JP3640980B2 (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998018484A1 (en) * 1996-10-31 1998-05-07 Toray Industries, Inc. Therapeutic agent and method for feline aids virus infections and feline atopic dermatitis
JP2001226287A (en) * 2000-02-17 2001-08-21 Sumitomo Pharmaceut Co Ltd Stable parenteral preparation
WO2004096264A1 (en) * 1997-10-30 2004-11-11 Tsunesuke Kajimoto Method for treating infection with feline leukemia virus
WO2006095433A1 (en) 2005-03-10 2006-09-14 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Therapeutic agent for bovine digestive system disease
WO2007037099A1 (en) 2005-09-27 2007-04-05 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Remedy for mastitis
WO2007037098A1 (en) 2005-09-27 2007-04-05 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Reproductive disorder remedy
JP2007528865A (en) * 2003-07-17 2007-10-18 エチファルム Coprecipitation active substance-containing particles

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998018484A1 (en) * 1996-10-31 1998-05-07 Toray Industries, Inc. Therapeutic agent and method for feline aids virus infections and feline atopic dermatitis
WO2004096264A1 (en) * 1997-10-30 2004-11-11 Tsunesuke Kajimoto Method for treating infection with feline leukemia virus
JP2001226287A (en) * 2000-02-17 2001-08-21 Sumitomo Pharmaceut Co Ltd Stable parenteral preparation
JP4536194B2 (en) * 2000-02-17 2010-09-01 大日本住友製薬株式会社 Stable injectable formulation
JP2007528865A (en) * 2003-07-17 2007-10-18 エチファルム Coprecipitation active substance-containing particles
JP4754485B2 (en) * 2003-07-17 2011-08-24 エチファルム Coprecipitation active substance-containing particles
WO2006095433A1 (en) 2005-03-10 2006-09-14 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Therapeutic agent for bovine digestive system disease
WO2007037099A1 (en) 2005-09-27 2007-04-05 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Remedy for mastitis
WO2007037098A1 (en) 2005-09-27 2007-04-05 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Reproductive disorder remedy

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