JPH02304029A - Clinical agent for diabetes - Google Patents
Clinical agent for diabetesInfo
- Publication number
- JPH02304029A JPH02304029A JP1123650A JP12365089A JPH02304029A JP H02304029 A JPH02304029 A JP H02304029A JP 1123650 A JP1123650 A JP 1123650A JP 12365089 A JP12365089 A JP 12365089A JP H02304029 A JPH02304029 A JP H02304029A
- Authority
- JP
- Japan
- Prior art keywords
- diabetes
- ifn
- gamma
- produced
- agent
- 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.)
- Pending
Links
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 26
- 108010074328 Interferon-gamma Proteins 0.000 claims abstract description 22
- 229960003130 interferon gamma Drugs 0.000 claims abstract description 5
- 102000008070 Interferon-gamma Human genes 0.000 claims description 4
- 229940126585 therapeutic drug Drugs 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 102100037850 Interferon gamma Human genes 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 5
- 230000006798 recombination Effects 0.000 abstract description 5
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 2
- 210000000496 pancreas Anatomy 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000001066 destructive effect Effects 0.000 abstract 1
- 210000003527 eukaryotic cell Anatomy 0.000 abstract 1
- 210000004153 islets of langerhan Anatomy 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 7
- 239000003814 drug Substances 0.000 description 5
- 239000003472 antidiabetic agent Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 229940127003 anti-diabetic drug Drugs 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 210000000207 lymphocyte subset Anatomy 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 101100438957 Mus musculus Cd8a gene Proteins 0.000 description 1
- 101001044384 Mus musculus Interferon gamma Proteins 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229940037525 nasal preparations Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Abstract
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は、糖尿病治療薬に関する。[Detailed description of the invention] [Industrial application field] TECHNICAL FIELD The present invention relates to a therapeutic drug for diabetes.
［従来の技術］
糖尿病治療薬に関しては従来から種々の報告がされてい
るが、糖尿病の治療効果および糖尿病の発症を抑える予
防効果の双方の効果を満足するものは未だ知られていな
い。[Prior Art] Although various reports have been made regarding antidiabetic drugs, there is still no known drug that satisfies both the therapeutic effect of diabetes and the preventive effect of suppressing the onset of diabetes.
優れた糖尿病治療薬としては、まず糖尿病の治療効果が
優れていることが重要であるが、同時に糖尿病の発症を
抑えること、インシュリンを分泌する膵臓ランゲルハン
ス島のβ細胞（以下、β細胞と略す）を破壊しないこと
も重要な要件である。For a good antidiabetic drug, it is important that it has an excellent therapeutic effect on diabetes, but at the same time, it is also important to suppress the onset of diabetes. It is also an important requirement not to destroy the
［発明が解決しようとする課題］
本発明は、糖尿病の治療効果に優れ、さらに糖尿病の発
症を抑え、β細胞を破壊しないという優れた糖尿病治療
薬を提供することを目的とする。[Problems to be Solved by the Invention] An object of the present invention is to provide an excellent antidiabetic drug that has an excellent therapeutic effect on diabetes, suppresses the onset of diabetes, and does not destroy β cells.
［課題を解決するための手段］ 上記目的は、以下の本発明により達成される。[Means to solve the problem] The above object is achieved by the present invention as described below.
すなわち、本発明は天然型インターフェロン−γまなは
その同効物を有効成分とする糖尿病治療薬である。That is, the present invention is a therapeutic drug for diabetes containing natural interferon-gamma or its equivalent as an active ingredient.
本発明で使用する天然型インターフェロン−γ（以下、
ＩＦＮ−γと略す）は、Ｔリンパ球が産生するもの、化
学合成により製造されるもの、遺伝子組換え技術により
製造される（特開昭６０＝２０２８９９号公報）のいず
れでも良いが、真核細胞を宿主として遺伝子組換え技術
により製造されるものが特に望ましい。Natural interferon-γ (hereinafter referred to as
IFN-γ) may be produced by T lymphocytes, produced by chemical synthesis, or produced by genetic recombination technology (Japanese Unexamined Patent Publication No. 202899), but it may be produced by eukaryotes. Particularly desirable are those produced by genetic recombination technology using cells as hosts.
また、本発明のＩＦＮ−γの同効物とは、ＩＦＮ−γ特
有の活性を有するものであれば全てを包含する。たとえ
ば、そのポリペプチド部分が天然に存在するインターフ
ェロン−γの配列を有するものや、そのＣ末端が欠損し
ているもの、あるいはそのアミノ酸残基が一部置換され
たものでも、ＩＦＮ−γ特有の活性を有するものは本発
明に含まれる。In addition, the term "substances with the same effect as IFN-γ" of the present invention includes all substances that have an activity specific to IFN-γ. For example, even if the polypeptide portion has the sequence of naturally occurring interferon-γ, its C-terminus is deleted, or some of its amino acid residues have been substituted, Those having activity are included in the present invention.
ＩＦＮ−γは、抗腫瘍作用等の生物活性を有する糖タン
パク質であるが、一方、それを産生した細胞と同じ動物
種の細胞および組織に対しては、有効な活性を与えるも
のの、他種の組織および細胞に対しては無効であったり
、弱い活性しか与えないという種特異性を有することが
知られている。IFN-γ is a glycoprotein that has biological activities such as antitumor effects.On the other hand, although it has effective activity against cells and tissues of the same animal species as the cells that produced it, it It is known to have species specificity, such as being ineffective or only having weak activity against tissues and cells.
従って、ヒトに投与されるＩＦＮ−γとしては、ヒトＩ
ＦＮ−γが用いられる。Therefore, as IFN-γ to be administered to humans, human I
FN-γ is used.
本発明のＩＦＮ−γは、公知の方法により製造、精製す
ることができる（たとえば、小林茂保編パインターフェ
ロンの科学′°講談社（１９８５）、特開昭６０−２０
２８９９号公報）。The IFN-γ of the present invention can be produced and purified by known methods (for example, Shigeyasu Kobayashi, ed., Science of Pine Interferon, Kodansha (1985), JP-A-60-20
Publication No. 2899).
本発明の治療薬は、ＩＦＮ−γの標本それ自体でも良く
、また安定剤、緩衝剤、希釈剤、等張剤、防腐剤等の賦
形剤を適宜混合して製剤化しても良い。The therapeutic agent of the present invention may be the IFN-γ specimen itself, or may be formulated by appropriately mixing excipients such as stabilizers, buffers, diluents, isotonic agents, and preservatives.
剤型としては、注射剤、カプセル剤、経鼻剤、生薬、経
口薬、軟膏剤等、種々の形態のものが用いられる。Various dosage forms can be used, such as injections, capsules, nasal preparations, herbal medicines, oral medicines, and ointments.
投与量は、投与対象、投与方法、症状等に応じ適宜決定
されるが、一般には１０万〜Ｆ、、０００万単位、特に
３０万〜３００万単位、１〜７凹／週の範囲で投与され
る。The dosage is determined as appropriate depending on the subject, administration method, symptoms, etc., but is generally administered in the range of 100,000 to 0,000,000 units, particularly 300,000 to 3,000,000 units, and 1 to 7 doses/week. be done.
本発明の糖尿病治療薬は、インシュリン依存性糖尿病で
ある■型糖尿病に特に有効である。The therapeutic agent for diabetes of the present invention is particularly effective for type 2 diabetes, which is insulin-dependent diabetes.
実験例１
■型糖尿病の自然発症モデル動物であるＮＯＤマウスを
用い、以下の方法によりＩＦＮ−γの顕性糖尿病の発症
に対する効果について実験しな。Experimental Example 1 Using NOD mice, which are spontaneous model animals for type 1 diabetes, an experiment was conducted to examine the effect of IFN-γ on the onset of overt diabetes by the following method.
２週令の雌ＮＯＤマウス１５匹に、週３回、２００週令
で５Ｘ１０４Ｕの遺伝子組み換え型マウスＩ ＦＮ−７
（Ｐｒｏｃ、 Ｎａｔｌ、 Ａｃａｄ、 ＳＣｉ、、
ｌｌ５Ａ靭、 ５８４２〜４．６（１９８３）に従い、
ＣＯＳ細胞を宿主として遺伝子組み換え技術により製造
した。〉を腹腔内に投与し、血糖、尿糖の測定を行ない
、２００週令に組織学的検索を行なった。対照群には０
゜２ｍｌの生理食塩水を投与した。また、実験終了時に
膵臓リンパ球サブセットの検索を行なった。なお、糖尿
病の発症はマウスの血糖が２００■／旧以上、かつ尿糖
陽性を示した場合、糖尿病発症とした。Fifteen 2-week-old female NOD mice received 5 x 104 U of genetically modified mouse I FN-7 three times a week at 200 weeks of age.
(Proc, Natl, Acad, SCi,...
According to Ill5A Utsu, 5842-4.6 (1983),
It was produced by genetic recombination technology using COS cells as a host. ) was administered intraperitoneally, blood sugar and urine sugar were measured, and histological examination was performed at 200 weeks of age. 0 for control group
2 ml of physiological saline was administered. Additionally, pancreatic lymphocyte subsets were searched at the end of the experiment. The onset of diabetes was determined when the mouse's blood sugar level was 200 ml or higher and the urine was positive for sugar.
結果を第１図に示す。対照群では、２００週令でに７０
〜８０％の個体で糖尿病の発症をみた。The results are shown in Figure 1. In the control group, at 200 weeks of age, 70
The onset of diabetes was observed in ~80% of individuals.
一方、ＩＦＮ−γ投与群は、２００週令でに２０％の個
体で糖尿病の発症をみたのみであった。On the other hand, in the IFN-γ administration group, only 20% of the animals developed diabetes at 200 weeks of age.
また、膵臓の組織学的検索では、ＩＦＮ−γ投与群、対
照群とも同程度の１ｎｓｕｌｉｔｉｓをみとめた。Furthermore, in histological examination of the pancreas, the same level of 1 nsulitis was observed in both the IFN-γ administration group and the control group.
Ｉｎ５ｕｌｉｔｉｓを構成している細胞は、■ＦＮ−γ
投与群も対照群と同じ（Ｔ ｈ ｙ −１陽性、Ｌ３Ｔ
４陽性細胞が主で、一部Ｔｈｙ−１陽性、Ｌｙｔ−２陽
性細胞も存在した。The cells that make up In5ulitis are ■FN-γ
The administration group is also the same as the control group (Thy-1 positive, L3T
The cells were mainly 4-positive, with some Thy-1-positive and Lyt-2-positive cells also present.
牌臓リンパ球ザブセットの検索では、ＩＦＮ−γ投与群
ではＴ ｈ ｙ−１，陽性、Ｌ ｙ−１陽性細胞が減少
していた。この結果を表−１に示す。A search for spleen lymphocyte subsets revealed that Th y-1, positive and Ly-1 positive cells decreased in the IFN-γ administration group. The results are shown in Table-1.
−５＝
−〇 −
実験例２
１２週令のＮＯＤマウス１群８匹に、週３回、３０週令
まで実験例１と同様に、５×１０４Ｕの遺伝子組み換え
型マウスＩＦＮ−γを腹腔内に投与し、３０週令までの
糖尿病発症率を調べた。対照群には０．２ｍｌの生理食
塩水を投与した。−5= −〇 − Experimental Example 2 5 × 104 U of genetically modified mouse IFN-γ was intraperitoneally administered to 12-week-old NOD mice in a group of 8 mice three times a week until they were 30 weeks old, in the same manner as in Experimental Example 1. The incidence of diabetes up to 30 weeks of age was investigated. The control group received 0.2 ml of physiological saline.
結果を第２図に示す。対照群では３０週令時までに８７
．５％の個体で糖尿病の発症を示したが、ＩＦＮ−γ投
与群の糖尿病発症率は５０％であった。The results are shown in Figure 2. 87 by 30 weeks of age in the control group.
．． Although 5% of individuals showed the onset of diabetes, the incidence of diabetes in the IFN-γ-treated group was 50%.
以上のことから、ＩＦＮ−γは顕性糖尿病の発症の抑制
に効果があることが示された。従って、β細胞の破壊は
、１．ＦＮ−γの投与により抑制されていることがわか
った。From the above, it was shown that IFN-γ is effective in suppressing the onset of overt diabetes. Therefore, the destruction of β cells is caused by 1. It was found that this was suppressed by administration of FN-γ.
［発明の効果］
本発明のＩＦＮ−γは、ＮＯＤマウスの糖尿病の発症に
抑制的に働くため、工型糖尿病発症の予防効果が優れて
おり、糖尿病治療薬として有用である。[Effects of the Invention] Since the IFN-γ of the present invention acts to suppress the onset of diabetes in NOD mice, it has an excellent preventive effect on the onset of industrial diabetes and is useful as a therapeutic agent for diabetes.
第１図および第２図は、本発明の糖尿病治療薬を投与し
たＮＯＤマウスと、投与しなかったＮＯＤマウスの糖尿
病発症を示すものであり、第１図は実験例１の結果を、
第２図は実験例２の結果を各々示す。Figures 1 and 2 show the onset of diabetes in NOD mice administered with the antidiabetic agent of the present invention and in NOD mice not administered, and Figure 1 shows the results of Experimental Example 1.
FIG. 2 shows the results of Experimental Example 2.
Claims (1)
有効成分とする糖尿病治療薬。(1) A therapeutic drug for diabetes containing natural interferon-γ or its equivalent as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1123650A JPH02304029A (en) | 1989-05-17 | 1989-05-17 | Clinical agent for diabetes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1123650A JPH02304029A (en) | 1989-05-17 | 1989-05-17 | Clinical agent for diabetes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02304029A true JPH02304029A (en) | 1990-12-17 |
Family
ID=14865857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1123650A Pending JPH02304029A (en) | 1989-05-17 | 1989-05-17 | Clinical agent for diabetes |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02304029A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0744949A1 (en) * | 1994-02-18 | 1996-12-04 | Georgetown University | Treatment and/or prevention of type i diabetes mellitus with gamma interferon administration |
-
1989
- 1989-05-17 JP JP1123650A patent/JPH02304029A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0744949A1 (en) * | 1994-02-18 | 1996-12-04 | Georgetown University | Treatment and/or prevention of type i diabetes mellitus with gamma interferon administration |
| EP0744949A4 (en) * | 1994-02-18 | 2000-03-01 | Univ Georgetown | Treatment and/or prevention of type i diabetes mellitus with gamma interferon administration |
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