JP2519954B2 - Diagnostic load test agent - Google Patents
Diagnostic load test agentInfo
- Publication number
- JP2519954B2 JP2519954B2 JP62296038A JP29603887A JP2519954B2 JP 2519954 B2 JP2519954 B2 JP 2519954B2 JP 62296038 A JP62296038 A JP 62296038A JP 29603887 A JP29603887 A JP 29603887A JP 2519954 B2 JP2519954 B2 JP 2519954B2
- Authority
- JP
- Japan
- Prior art keywords
- concentration
- test agent
- load test
- weight
- administration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000012360 testing method Methods 0.000 title claims description 15
- MPCAJMNYNOGXPB-SLPGGIOYSA-N 1,5-anhydro-D-glucitol Chemical compound OC[C@H]1OC[C@H](O)[C@@H](O)[C@@H]1O MPCAJMNYNOGXPB-SLPGGIOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 description 58
- 206010012601 diabetes mellitus Diseases 0.000 description 17
- 241000700159 Rattus Species 0.000 description 16
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229960001052 streptozocin Drugs 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- -1 organic acid salts Chemical class 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 2
- 229960000367 inositol Drugs 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007791 dehumidification Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、1,5−アンヒドログルシトール（以下、AG
という）を含有する負荷試験剤に関するものであり、AG
を負荷することによって、糖尿病の診断を容易にするた
めに使用するものである。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention is directed to 1,5-anhydroglucitol (hereinafter referred to as AG
The load test agent containing
Is used to facilitate the diagnosis of diabetes.
AGは、ヒト髄液及び血漿中に存在し、ある種の疾患、
特に糖尿病において、血漿中の濃度が低下することが報
告されている化合物で、糖尿病のマーカーとして期待さ
れているものである。（日本臨牀、44巻、夏季臨時増刊
号、546（1986））。AG is present in human cerebrospinal fluid and plasma and is associated with certain diseases,
In particular, it is a compound that is reported to have a reduced plasma concentration in diabetes and is expected as a marker for diabetes. (Nihon Rinjo, Vol. 44, Summer Extra Edition, 546 (1986)).
しかし血漿中のAG濃度は正常者でも人によって約10−
50μg/mlと大きくばらつき、一方糖尿病者でもその濃度
が０〜約10μg/mlとばらつくので、通常の状態で血漿中
のAG濃度を測定しただけでは、正常者か、糖尿病者か、
判断できない場合がある。However, the AG concentration in plasma is about 10-
There is a large variation of 50 μg / ml, and even in diabetic patients, the concentration varies from 0 to about 10 μg / ml, so it is normal or diabetic if the AG concentration in plasma is measured under normal conditions.
It may not be possible to judge.
一方、糖尿病の診断に糖負荷試験の結果が広く利用さ
れているが、この負荷試験ではグルコース負荷後の血中
グルコース濃度の変化（インスリン作用）を経時的に追
跡するものであるから、頻回の採血と測定が必要とな
る。On the other hand, the results of the glucose tolerance test are widely used for the diagnosis of diabetes, but in this tolerance test, changes in blood glucose concentration (insulin action) after glucose load are followed over time, and therefore frequently. Blood collection and measurement are required.
そこで本発明者らは種々検討した結果、正常ラツトに
AGに投与すると即ち、AG負荷を与えると投与前の血漿中
のAG濃度の高低に関係なく濃度が上昇し、一定時間後に
負荷前より高い一定の濃度を示すこと、一方糖尿病ラツ
トにAG負荷を与えると負荷直後はその濃度が上昇するも
のの一定時間後はもとの濃度にもどってしまうこと、従
って、AG負荷により正常者のAG濃度と糖尿病者のそれと
の差が広がり、負荷後１回のAG濃度の測定で診断が可能
となりAGが負荷試験剤として有用なことを見い出した。Therefore, as a result of various investigations by the present inventors, a normal rat was obtained.
When administered to AG, that is, when an AG load is applied, the concentration increases regardless of whether the AG concentration in plasma before administration is high, and after a certain period of time, it shows a constant concentration higher than that before the load, while the AG rat is loaded with the AG load. When given, the concentration increases immediately after the load, but after a certain period of time, it returns to the original concentration. Therefore, the difference between the AG concentration of the normal person and that of the diabetic person widens due to the AG load. We found that AG is useful as a stress test agent because it enables diagnosis by measuring AG concentration.
本発明は上記知見に基づき完成されたものである。即
ち、本発明はAGを有効成分とする診断用負荷試験剤に関
する。The present invention has been completed based on the above findings. That is, the present invention relates to a diagnostic load test agent containing AG as an active ingredient.
本発明で使用するAGは公知の物質で、その製法は例え
ば、ジヤーナル オブ ザ アメリカン ケミカルソサ
イエテイー（J.Am.Chem.Soc）71巻3679−81ページ、194
9年に記載されている。又、そのLD50値は本発明者らの
測定によるとラツトへの経口投与で29.7g/Kgであった。AG used in the present invention is a known substance, and its production method is described in, for example, Journal of the American Chemical Society (J. Am. Chem. Soc), Vol. 71, pages 3679-81, 194.
Listed in 9 years. The LD 50 value was 29.7 g / Kg when orally administered to the rat according to the measurement by the present inventors.
本発明で用いられる負荷試験剤は、AGが単独または賦
形剤あるいは担体と混合して、投与経路に応じて、経口
剤、注射剤、坐剤などとして作成される。賦形剤及び担
体としては、薬剤学的に許容されるものが選ばれ、その
種類及び組成は、投与経路や投与方法によって決まる。
例えば、液状担体として水、アルコールもしくは大豆
油、ピーナツ油、ゴマ油、ミネラル油等の動植物油、ま
たは合成油が用いられる。固体担体としてマルトース、
シユクロースなどの糖類、アミノ酸類、ヒドロキシプロ
ピルセルロースなどのセルロース誘導体、ステアリン酸
マグネシウムなどの有機酸塩などが使用される。注射剤
の場合一般に水、生理食塩水、各種緩衝液、グルコー
ス、イノシツトール、マンニトール等の糖類溶液、エチ
レングリコール、ポリエチレングリコール等のグリコー
ル類が望ましい。また、イノシトール、マンニトール、
グルコース、マンノース、マルトース、シユクロース等
の糖類、フエニルアラニン等のアミノ酸類の賦形剤と共
に凍結乾燥製剤とし、それを投与時に注射用の適当な溶
剤、例えば滅菌水、生理食塩水、ブドウ糖液、電解質溶
液、アミノ酸等の静脈投与用液体に溶解して投与するこ
ともできる。経口剤の場合、一般に水、炭酸水に溶解
し、食添として許容されている各種物質により飲み易い
ように加工された液剤、前記固体担体もしくは液状担体
とともに錠剤、カプセル剤、粉剤、顆粒剤、液剤、ドラ
イシロツプ剤等の形態で用いられる。The stress test agent used in the present invention is prepared as an oral agent, an injectable agent, a suppository, etc., depending on the administration route, by mixing AG alone or with an excipient or a carrier. As the excipient and carrier, those which are pharmaceutically acceptable are selected, and the type and composition thereof are determined by the administration route and administration method.
For example, water, alcohol or soybean oil, animal and vegetable oils such as peanut oil, sesame oil and mineral oil, or synthetic oil is used as the liquid carrier. Maltose as a solid carrier,
Sugars such as sucrose, amino acids, cellulose derivatives such as hydroxypropyl cellulose, and organic acid salts such as magnesium stearate are used. In the case of an injection, water, physiological saline, various buffer solutions, saccharide solutions such as glucose, inositol and mannitol, and glycols such as ethylene glycol and polyethylene glycol are generally preferable. Also, inositol, mannitol,
Glucose, mannose, maltose, sugars such as sucrose, and a freeze-dried preparation together with excipients of amino acids such as phenylalanine, a suitable solvent for injection at the time of administration, such as sterile water, physiological saline, glucose solution, It can also be administered by dissolving it in an electrolyte solution or a liquid for intravenous administration such as amino acid. In the case of an oral agent, a liquid agent which is generally dissolved in water or carbonated water and processed to be easy to drink by various substances which are allowed as a food additive, tablets, capsules, powders, granules together with the solid carrier or liquid carrier, It is used in the form of liquid preparations, dry syrup preparations and the like.
製剤中におけるAGの含量は製剤により種々に異なる
が、通常0.01〜100重量％、好ましくは0.1〜100重量％
である。例えば、注射液の場合には、通常0.1〜５重量
％の本化合物を含むようにすることがよい。経口用液剤
の場合0.1〜10重量％が良い。カプセル剤、錠剤、顆粒
剤、粉剤の場合は、一般に本化合物の含量は約３〜100
重量％、好ましくは５〜100重量％であり、残部は担体
である。The content of AG in the preparation varies depending on the preparation, but is usually 0.01 to 100% by weight, preferably 0.1 to 100% by weight.
Is. For example, in the case of an injection solution, it is usually preferable to contain 0.1 to 5% by weight of the present compound. In the case of oral liquid preparation, 0.1-10% by weight is preferable. In the case of capsules, tablets, granules and powders, the content of this compound is generally about 3-100.
% By weight, preferably 5 to 100% by weight, the balance being the carrier.
投与量は、患者の年齢、体重、検査目的により決定さ
れるが、１回当りの負荷量は、大人の場合一般に、0.1
〜10g/人で、負荷による変化が明確に確認できる量が必
要であり、５〜50mg/Kgが好ましい。The dose is determined by the patient's age, weight, and the purpose of the test, but the dose per administration is generally 0.1 for adults.
The amount is required to be clearly confirmed at 10 to 10 g / person, and it is preferably 5 to 50 mg / Kg.
糖尿病診断の方法としては、AG負荷前後の体液中又は
尿中のAG濃度の変化、又は尿中への排泄量の変化を追跡
するものであれば、どの様な方法であっても良い。ま
た、負荷後、一定時間の蓄尿を行ない、その尿中のAG総
量から判断しても良い。たとえば、AGを経口的に負荷し
た場合、体内への吸収が起こり、投与前後の変化が安定
かつ最も大きくなる様、一定時間経過後に採血と採尿、
又は、いずれか一方のサンプリングを行ない、サンプル
中のAG濃度を適当な方法により測定すればよい。As a method for diagnosing diabetes, any method may be used as long as it tracks changes in AG concentration in body fluid or urine before or after AG loading, or changes in excretion into urine. It is also possible to collect urine for a certain period of time after loading and judge from the total amount of AG in the urine. For example, when AG is orally loaded, absorption into the body occurs and blood and urine collection after a certain period of time so that the change before and after administration is stable and maximizes.
Alternatively, either one may be sampled and the AG concentration in the sample may be measured by an appropriate method.
また、AGを負荷する方法は、AGを明確に体内に投与で
きるものであれば、どの様な方法であっても良い。たと
えば、経口的に、もしくは静注、点滴静注、筋注などの
注射により行なうことができる。より好ましくは、患者
に対する負担の少ない経口的な方法が好ましい。The method of loading AG may be any method as long as AG can be clearly administered into the body. For example, it can be performed orally or by injection such as intravenous injection, intravenous drip injection, and intramuscular injection. More preferably, an oral method that causes less burden on the patient is preferable.
次にAGが負荷試験剤として有用なことを試験例により
具体的に説明する。Next, the usefulness of AG as a load test agent will be specifically described with reference to test examples.
試験例１ （AG負荷試験による血中AG濃度の変化） ＜糖尿病ラツトの作成＞ ウインスター系のラツト（雄、体重250g）に、ストレ
プトゾトシン（STZ）を、45mg/Kgとなる様に1mMクエン
酸バツフアー（pH4.5）0.5mlに溶解し、尾静脈より注入
して、STZ糖尿病ラツトを作成した。糖尿病発症ラツト
は、安定化のために、STZ投与後１週間を経過してから
実験に使用した。Test Example 1 (Change in blood AG concentration by AG load test) <Preparation of diabetic rat> Winstar rat (male, body weight: 250 g) was supplemented with streptozotocin (STZ) at 45 mg / Kg at 1 mM citric acid. A STZ diabetic rat was prepared by dissolving it in 0.5 ml of buffer (pH 4.5) and injecting it from the tail vein. The diabetic rats were used for the experiment one week after the STZ administration for stabilization.
＜AG負荷試験＞ 同一ロツトの餌で長期間飼育して来た正常及びSTZで
発症した糖尿病のラツト（ウインスター系、雄、体重25
0g）各４匹ずつに、生理食塩水で溶解した15mg/ml濃度
のAG溶液を、50mg/Kgとなる様に経口投与した。投与
後、経時的に採血を行ない、血漿中のAG濃度を測定し
た。各時間におけるAG濃度の平均を求め、その推移を第
１図に示した。<AG load test> Rats with normal and STZ-induced diabetes that had been bred for a long time on the same lot food (Winster system, male, body weight 25)
0g) An AG solution having a concentration of 15 mg / ml dissolved in physiological saline was orally administered to each of 4 animals so as to have a concentration of 50 mg / Kg. After administration, blood was collected over time to measure the AG concentration in plasma. The average AG concentration at each time was calculated, and the transition thereof is shown in FIG.
図から明らかな様に、負荷したAGは、効率良く体内に
取り込まれ、0.5〜１時間後に最高濃度を示した。その
後徐々に低下し、24時間後には、ほぼ一定濃度となり、
その後48時間以上安定していた。負荷後のAG濃度の正常
と糖尿病ラツトの差は、負荷前のAG濃度の差より、どの
時点においても２〜５倍と大幅に拡大していた。As is clear from the figure, the loaded AG was efficiently taken up in the body and showed the maximum concentration after 0.5 to 1 hour. After that, the concentration gradually decreased, and after 24 hours, the concentration became almost constant,
It was stable for more than 48 hours after that. The difference between the normal AG concentration and the diabetic rat after loading was 2 to 5 times larger than the difference in the AG concentration before loading at any time.
試験例２ 血中AG濃度の高い群及び低い群の２群の中から、それ
ぞれ３匹ずつのラツトを無行為に選び出し、試験例１と
同様にしてSTZ糖尿病ラツトを作成した。これら各群３
匹の正常及び糖尿病ラツトに、5mg/ml濃度となる様に生
理食塩水に溶解したAG溶液1mlを経口投与した。投与後2
4時間後に各ラツトの血液を採取し、血漿中のAG濃度を
測定しその結果を表１に示した。表の結果から明らかな
様に、AGの負荷により、正常ラツト間の血中AG濃度がほ
ぼ等しくなつた。また、AG値の低い群における正常と糖
尿病ラツト間の差も、AG負荷により拡大し、安定に評価
できる様になった。Test Example 2 From each of two groups, a group having a high blood AG concentration and a group having a low blood AG concentration, three rats each were inadvertently selected, and an STZ diabetic rat was prepared in the same manner as in Test Example 1. Each of these groups 3
Normal and diabetic rats were orally administered with 1 ml of AG solution dissolved in physiological saline so as to have a concentration of 5 mg / ml. 2 after administration
Blood was collected from each rat 4 hours later, and the AG concentration in plasma was measured. The results are shown in Table 1. As is clear from the results shown in the table, the AG concentration in the blood between the normal rats was almost equal due to the loading of AG. In addition, the difference between normal and diabetic rats in the group with a low AG value was expanded by the AG load, and stable evaluation became possible.
製剤例１ （内服液剤） AG20重量部に対し、精製水を加え全量を400部とし
て、これを溶解後ミリポアフイルターGSタイプを用いて
除菌過した。この液40mlを50mlのバイアル瓶にと
り、密封して、内服液剤を得た。 Formulation Example 1 (Internal Solution) To 20 parts by weight of AG, purified water was added to bring the total amount to 400 parts, and after dissolving this, the bacteria were sterilized using Millipore Filter GS type. 40 ml of this solution was placed in a 50 ml vial and sealed to obtain an internal liquid preparation.
製剤例２ （散剤） AGを粉砕して微粉末とし、2gずつ除湿用ラミネート紙
で作った袋に封入し、入口を熱圧着してシールした。Formulation Example 2 (Powder) AG was pulverized into a fine powder, and 2 g each was enclosed in a bag made of laminated paper for dehumidification, and the inlet was thermocompression-bonded and sealed.
製剤例３ （顆粒剤） AG500重量部、結晶セルロース330部及びヒドロキシプ
ロピルセルロース20部をよく混和し、ロール型圧縮機
（ローラーコンバクター ）を用いて圧縮し、破砕し
て、16メツシユと60メツシユの間に入るよう篩過し、顆
粒とした。Formulation Example 3 (granules) 500 parts by weight of AG, 330 parts of crystalline cellulose and hydroxyp
A roll-type compressor that mixes 20 parts of ropyl cellulose well
(Roller compactor ) And crush
Sieving to fit between 16 and 60 mesh
It was made into grains.
製造例４ （注射剤） AG40重量部に対し、精製水を加え全量を400部とし
て、これを溶解後ミリポアフイルターGSタイプを用いて
除菌過した。この液20mlを30mlのバイアル瓶にと
り、密封して、１バイアルにAG2gを含む注射剤を得た。Production Example 4 (Injection) Purified water was added to 40 parts by weight of AG to make 400 parts in total, and after dissolving this, the bacteria were sterilized by using Millipore Filter GS type. 20 ml of this solution was placed in a 30 ml vial and sealed to obtain an injection containing 2 g of AG in 1 vial.
製剤例５ （錠剤） AG60重量部、結晶乳糖90部、結晶セルロース147部、
及びステアリン酸マグネシウム３部をＶ型混合機で混合
の後、打錠し、１錠600mgの錠剤を得た。Formulation Example 5 (tablet) AG 60 parts by weight, crystalline lactose 90 parts, crystalline cellulose 147 parts,
And 3 parts of magnesium stearate were mixed in a V-type mixer and then tableted to obtain 600 mg tablets.
第１図は、正常及び糖尿病ラツトにAGを負荷後、血中の
濃度の変化を経時的に測定したものである。 FIG. 1 shows the change in blood concentration after the AG was loaded on normal and diabetic rats, which was measured over time.
Claims (1)
とする診断用負荷試験剤。1. A diagnostic load test agent comprising 1,5-anhydroglucitol as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62296038A JP2519954B2 (en) | 1987-11-26 | 1987-11-26 | Diagnostic load test agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62296038A JP2519954B2 (en) | 1987-11-26 | 1987-11-26 | Diagnostic load test agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01139535A JPH01139535A (en) | 1989-06-01 |
| JP2519954B2 true JP2519954B2 (en) | 1996-07-31 |
Family
ID=17828298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62296038A Expired - Lifetime JP2519954B2 (en) | 1987-11-26 | 1987-11-26 | Diagnostic load test agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2519954B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2010106871A1 (en) * | 2009-03-19 | 2012-09-20 | 国立大学法人富山大学 | Osmotic pressure regulator |
-
1987
- 1987-11-26 JP JP62296038A patent/JP2519954B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01139535A (en) | 1989-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Curry et al. | Factors affecting chlorpromazine plasma levels in psychiatric patients | |
| EP0083108B1 (en) | Aqueous solution containing ubidecarenone | |
| Patel et al. | Use of liposomes to aid intestinal absorption of entrapped insulin in normal and diabetic dogs | |
| EP0233559B1 (en) | Readily absorbable pharmaceutical composition | |
| Blanchard et al. | Comparative pharmacokinetics of caffeine in young and elderly men | |
| Lalka et al. | Kinetics of the oral antiarrhythmie lidocaine congener, tocainide | |
| Bergstrom et al. | Penicillamine kinetics in normal subjects | |
| JP2003508436A (en) | Pharmaceutical stable oxaliplatinum formulation for parenteral administration | |
| McNamara et al. | Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk. | |
| JP2519954B2 (en) | Diagnostic load test agent | |
| Raghow et al. | High-performance liquid chromatographic assay of tolbutamide and carboxytolbutamide in human plasma | |
| Lin et al. | Urinary excretion kinetics of famotidine in rats. | |
| Gouyon et al. | Urinary excretion of N-acetyl-glucosaminidase and beta-2-microglobulin as early markers of gentamicin nephrotoxicity in neonates | |
| PANCHAGNULA et al. | Transdermal delivery of azidothymidine (AZT) through rat skin ex‐vivo | |
| PETERSEN et al. | Digoxin–trimethoprim interaction | |
| JOHNSON et al. | The influences of rate of injection upon the effects of diazoxide | |
| EP0290817B1 (en) | A use of oxetanocin for inhibiting hiv | |
| EP0005733B1 (en) | Pharmaceutical compositions for use in the treatment of diabetic nephropathy and method for preparing them | |
| Dan et al. | Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women | |
| TESAN | Excretion of clofazimine in human milk in leprosy patients | |
| Gower et al. | Serum and blood concentration of sodium cephalexin in man given single intramuscular and intravenous injections | |
| Wood et al. | Ticrynafen: kinetics, protein binding, and effects on serum and urinary uric acid | |
| JP3285198B2 (en) | Liquid for internal use | |
| JP2643340B2 (en) | Human acquired immunodeficiency syndrome virus infection inhibitor | |
| Perucca et al. | Oxiracetam pharmacokinetics following single and multiple dose administration in the elderly |