JP6630115B2 - Pharmaceutical composition for reducing weight loss after extirpative surgery - Google Patents
Pharmaceutical composition for reducing weight loss after extirpative surgery Download PDFInfo
- Publication number
- JP6630115B2 JP6630115B2 JP2015213481A JP2015213481A JP6630115B2 JP 6630115 B2 JP6630115 B2 JP 6630115B2 JP 2015213481 A JP2015213481 A JP 2015213481A JP 2015213481 A JP2015213481 A JP 2015213481A JP 6630115 B2 JP6630115 B2 JP 6630115B2
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- composition according
- organ
- removal
- tissue
- 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.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 83
- 230000004580 weight loss Effects 0.000 title claims description 29
- 238000001356 surgical procedure Methods 0.000 title claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 210000000056 organ Anatomy 0.000 claims description 36
- 210000001519 tissue Anatomy 0.000 claims description 35
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 13
- 229910001882 dioxygen Inorganic materials 0.000 claims description 13
- 239000011261 inert gas Substances 0.000 claims description 13
- 230000037396 body weight Effects 0.000 claims description 9
- 210000003734 kidney Anatomy 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 210000004072 lung Anatomy 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 206010053942 Cerebral haematoma Diseases 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 210000004100 adrenal gland Anatomy 0.000 claims description 3
- 210000004204 blood vessel Anatomy 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 201000001883 cholelithiasis Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 210000002249 digestive system Anatomy 0.000 claims description 3
- 210000000750 endocrine system Anatomy 0.000 claims description 3
- 210000000232 gallbladder Anatomy 0.000 claims description 3
- 208000001130 gallstones Diseases 0.000 claims description 3
- 210000002216 heart Anatomy 0.000 claims description 3
- 210000002429 large intestine Anatomy 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 210000003205 muscle Anatomy 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 210000004560 pineal gland Anatomy 0.000 claims description 3
- 210000004994 reproductive system Anatomy 0.000 claims description 3
- 210000002345 respiratory system Anatomy 0.000 claims description 3
- 230000001953 sensory effect Effects 0.000 claims description 3
- 210000000813 small intestine Anatomy 0.000 claims description 3
- 210000000952 spleen Anatomy 0.000 claims description 3
- 210000003437 trachea Anatomy 0.000 claims description 3
- 230000002485 urinary effect Effects 0.000 claims description 3
- 210000004291 uterus Anatomy 0.000 claims description 3
- 206010062767 Hypophysitis Diseases 0.000 claims description 2
- 210000001198 duodenum Anatomy 0.000 claims description 2
- 210000003238 esophagus Anatomy 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 230000008520 organization Effects 0.000 claims description 2
- 230000000849 parathyroid Effects 0.000 claims description 2
- 210000003635 pituitary gland Anatomy 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 239000007789 gas Substances 0.000 description 29
- 241000700159 Rattus Species 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000013059 nephrectomy Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 230000002980 postoperative effect Effects 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 229910001873 dinitrogen Inorganic materials 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010015548 Euthanasia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 238000004880 explosion Methods 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 231100000037 inhalation toxicity test Toxicity 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010061825 Duodenal neoplasm Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 208000032376 Lung infection Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- 241000720974 Protium Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010054184 Small intestine carcinoma Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 239000003994 anesthetic gas Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 201000000312 duodenum cancer Diseases 0.000 description 1
- 238000013171 endarterectomy Methods 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 208000025661 ovarian cyst Diseases 0.000 description 1
- -1 oxygen radicals Chemical class 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000010579 uterine corpus leiomyoma Diseases 0.000 description 1
- 201000007954 uterine fibroid Diseases 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、水素ガスを含む医薬組成物、典型的には、器官または組織の摘出による体重減少を軽減するための気体状医薬組成物に関する。 The present invention relates to a pharmaceutical composition comprising hydrogen gas, typically a gaseous pharmaceutical composition for reducing weight loss due to removal of an organ or tissue.
手術侵襲は、医原性の外傷であり、様々な生体反応を引き起こすことが知られている。かかる生体反応は、手術後の患者の回復に大きく影響していると考えられる。手術侵襲の中でも、手術後の体重減少は、患者の予後に影響を与える重要な要素の１つである。例えば、がん患者など、器官または組織の摘出が伴う手術を受けた患者は、術後の炎症および発熱、術前または術後の身体的または精神的ストレス、食欲減衰など、様々な要因により、体重が急激に減少することが知られている。このような、手術後の体重減少は、患者にとって体力的および精神的に負担がかかるため、早期に回復させる薬剤が求められている。 Surgical invasion is an iatrogenic trauma and is known to cause various biological reactions. It is considered that such a biological reaction greatly affects the recovery of the patient after the operation. Among the surgical insults, post-operative weight loss is one of the key factors affecting patient prognosis. For example, patients who have undergone surgery involving the removal of organs or tissues, such as cancer patients, can have a variety of factors, including post-operative inflammation and fever, pre- or post-operative physical or mental stress, and reduced appetite. It is known that weight is rapidly reduced. Such a post-operative weight loss imposes a physical and mental burden on the patient, and there is a need for a drug that recovers early on.
分子状水素は、これまでに、酸素ラジカルのスカベンジャーとして有用であること（非特許文献１）、およびそのようなフリーラジカルスカベンジャーとしての性質を利用して、虚血再灌流障害を治療することが報告されている（特許文献１、非特許文献２）。また、分子状水素には、抗炎症効果など、多面的な効果があることが報告されている。 To date, molecular hydrogen has been useful as a scavenger for oxygen radicals (Non-Patent Document 1), and its properties as a free radical scavenger have been used to treat ischemia-reperfusion injury. It has been reported (Patent Document 1, Non-Patent Document 2). In addition, it has been reported that molecular hydrogen has various effects such as an anti-inflammatory effect.
一方、分子状水素がどのように多面的な効果を発揮するか、その作用機序は未だに明らかにされていない。 On the other hand, how molecular hydrogen exerts a multifaceted effect has not yet been elucidated.
本発明は、器官または組織の摘出による体重減少を軽減するために有用な医薬組成物を提供することを目的とする。 An object of the present invention is to provide a pharmaceutical composition useful for reducing weight loss due to removal of an organ or tissue.
本発明者らは、ラット５／６腎摘モデルの腎不全に対する分子状水素の影響を調査する過程で、意外にも、水素ガスを吸入させた場合に、腎摘後のラットの体重減少を顕著に軽減できることを見出し、本発明を完成させるに至った。 In the process of investigating the effect of molecular hydrogen on renal failure in a rat 5/6 nephrectomy model, the present inventors surprisingly found that the weight of rats after nephrectomy was reduced when hydrogen gas was inhaled. They have found that they can be significantly reduced, and have completed the present invention.
本発明は、上記の知見に基づくものであり、以下の特徴を包含する。
［１］水素ガスを含む気体状医薬組成物であって、
器官または組織の摘出による体重減少を軽減するための、
医薬組成物。
［２］［１］に記載の医薬組成物であって、
酸素ガスをさらに含むことを特徴とする、
医薬組成物。
［３］［１］または［２］に記載の組成物であって、
不活性ガスをさらに含むことを特徴とする、
医薬組成物。
［４］［１］〜［３］のいずれかに記載の医薬組成物であって、
前記水素ガスの濃度が、１〜４％（ｖ／ｖ）である
ことを特徴とする、
医薬組成物。
［５］［２］または［３］のいずれかに記載の医薬組成物であって、
前記水素ガスの濃度が、１〜４％（ｖ／ｖ）であり、
前記酸素ガス濃度が２１〜９９％（ｖ／ｖ）である
ことを特徴とする、
医薬組成物。
［６］［１］〜［５］のいずれかに記載の医薬組成物であって、
１日あたり０．５〜２４時間投与される
ことを特徴とする、
医薬組成物。
［７］［１］〜［６］のいずれかに記載の医薬組成物であって、
手術日後少なくとも１日以上投与される
ことを特徴とする、
医薬組成物。
［８］［１］〜［７］のいずれかに記載の医薬組成物であって、
手術前、および／または、手術中において投与される
ことを特徴とする、
医薬組成物。
［９］［１］〜［８］のいずれかに記載の医薬組成物であって、
前記「器官または組織の摘出」が癌、腫瘍、胆石、挫滅した組織の摘出；肺感染症による肺切除；弁置換、弁形成、大血管置換術、慢性肺血栓塞栓症に対する血栓内膜剥皮術；脳内血腫の除去；大腿骨頭置換術；またはドナーからの臓器摘出に伴う
ことを特徴とする、
医薬組成物。
［１０］［１］〜［９］のいずれかに記載の医薬組成物であって、
前記「器官または組織」が、循環器系：消化器系；呼吸器系；神経系；生殖器系；泌尿器；内分泌系；感覚器系；運動器系；乳房；または皮膚からなる群から選ばれる器官または組織の全部または一部である
ことを特徴とする、
医薬組成物。
［１１］［１］〜［９］のいずれかに記載の医薬組成物であって、
前記「器官または組織」が、大血管、心臓、食道、胃、十二指腸、小腸、大腸、脾臓、胆嚢、膵臓、肝臓、気管、肺、脳、子宮、卵巣、腎臓、甲状腺、副甲状腺、下垂体、副腎、ランゲルハンス島、松果体、眼、耳、骨、筋肉、乳房、および皮膚からなる群から選ばれる器官または組織の全部または一部である
ことを特徴とする、
医薬組成物。
［１２］［１］〜［１１］のいずれかに記載の医薬組成物であって、
水素ガスを投与しない場合との比較において、器官または組織の摘出後の最大体重減少を、３０％以上軽減することを特徴とする、
医薬組成物。
The present invention is based on the above findings and includes the following features.
[1] A gaseous pharmaceutical composition containing hydrogen gas,
To reduce weight loss due to removal of organs or tissues,
Pharmaceutical composition.
[2] The pharmaceutical composition according to [1],
Characterized by further containing oxygen gas,
Pharmaceutical composition.
[3] The composition according to [1] or [2],
Characterized by further comprising an inert gas,
Pharmaceutical composition.
[4] The pharmaceutical composition according to any one of [1] to [3],
The concentration of the hydrogen gas is 1 to 4% (v / v).
Pharmaceutical composition.
[5] The pharmaceutical composition according to any of [2] or [3],
A concentration of the hydrogen gas is 1 to 4% (v / v);
The oxygen gas concentration is 21 to 99% (v / v),
Pharmaceutical composition.
[6] The pharmaceutical composition according to any one of [1] to [5],
Characterized in that it is administered for 0.5 to 24 hours per day,
Pharmaceutical composition.
[7] The pharmaceutical composition according to any one of [1] to [6],
Characterized by being administered at least one day after the operation day,
Pharmaceutical composition.
[8] The pharmaceutical composition according to any one of [1] to [7],
Characterized in that it is administered before surgery and / or during surgery.
Pharmaceutical composition.
[9] The pharmaceutical composition according to any one of [1] to [8],
Removal of cancer, tumor, gallstones, or crushed tissue; removal of lungs due to pulmonary infection; valve replacement, valvuloplasty, large vessel replacement, thrombus intimal stripping for chronic pulmonary thromboembolism Removal of intracerebral hematoma; femoral head replacement; or with removal of an organ from a donor;
Pharmaceutical composition.
[10] The pharmaceutical composition according to any one of [1] to [9],
Said organ or tissue is an organ selected from the group consisting of circulatory system: digestive system; respiratory system; nervous system; reproductive system; urinary system; endocrine system; sensory system; Or being all or part of an organization,
Pharmaceutical composition.
[11] The pharmaceutical composition according to any one of [1] to [9],
The `` organ or tissue '' is a large blood vessel, heart, esophagus, stomach, duodenum, small intestine, large intestine, spleen, gallbladder, pancreas, liver, trachea, lung, brain, uterus, ovary, kidney, thyroid, parathyroid, pituitary , Adrenal glands, islets of Langerhans, pineal gland, eyes, ears, bones, muscles, breasts, and all or part of an organ or tissue selected from the group consisting of skin,
Pharmaceutical composition.
[12] The pharmaceutical composition according to any one of [1] to [11],
The method is characterized in that the maximum body weight loss after removal of an organ or tissue is reduced by 30% or more as compared with a case where hydrogen gas is not administered.
Pharmaceutical composition.
上記に挙げた本発明の態様の一または複数を任意に組み合わせた発明も、本発明の範囲に含まれる。 An invention obtained by arbitrarily combining one or more of the above-described aspects of the present invention is also included in the scope of the present invention.
本発明によれば、器官または組織の摘出による体重減少を軽減するために有用な医薬組成物が提供される。 According to the present invention, there is provided a pharmaceutical composition useful for reducing weight loss due to removal of an organ or tissue.
以下、本発明の実施の形態を具体的に説明する。 Hereinafter, embodiments of the present invention will be specifically described.
本発明において、「器官または組織の摘出による体重減少」とは、器官または組織の摘出手術によって惹起される手術後の体重減少を指す。したがって、器官または組織の摘出行為自体、すなわち器官または組織の摘出部位に起因する重量の減少は、本発明における「器官または組織の摘出による体重減少」には該当しない。 In the present invention, “weight loss due to removal of an organ or tissue” refers to weight loss after surgery caused by surgery to remove an organ or tissue. Therefore, the act of removing the organ or tissue itself, that is, the weight loss caused by the site where the organ or tissue is removed, does not fall under the “weight loss by removing the organ or tissue” in the present invention.
本発明の一実施形態において、器官または組織の摘出は、これに限定されるものではないが、手術後から一定の期間にわたって惹起される体重減少であって、全体重の少なくとも５％の減少、好ましくは全体重の少なくとも１０％の減少、より好ましくは全体重の少なくとも１５％の減少、より好ましくは全体重の少なくとも２０％の減少を引き起こすものである。 In one embodiment of the present invention, the removal of an organ or tissue is, but is not limited to, a weight loss caused over a period of time after surgery, wherein the weight loss is at least 5% of the total weight, Preferably, it causes at least a 10% reduction in total weight, more preferably at least a 15% reduction in total weight, more preferably at least a 20% reduction in total weight.
本発明の一実施形態において、「器官または組織の摘出」は、これに限定されるものではないが、悪性黒色腫、腎臓癌、前立腺癌、膀胱癌、乳癌、肺癌、膵臓癌、大腸癌、小腸癌、肝細胞癌、胆道癌、胃癌、卵巣癌、食道癌、十二指腸癌、皮膚癌、喉頭癌、咽頭癌、口腔内の癌などの固形がんの摘出；子宮筋腫、卵巣嚢腫、肺腫瘍、乳房腫瘍、結腸腫瘍、脳腫瘍などの各種の腫瘍の摘出；胆石の摘出；挫滅した組織の摘出；肺感染症による肺切除；弁置換、弁形成、大血管置換術、慢性肺血栓塞栓症に対する血栓内膜剥皮術；脳内血腫の除去；大腿骨頭置換術；ドナー（臓器提供者）からの臓器摘出、などに伴うものであり得る。 In one embodiment of the present invention, “extraction of an organ or tissue” includes, but is not limited to, malignant melanoma, kidney cancer, prostate cancer, bladder cancer, breast cancer, lung cancer, pancreatic cancer, colon cancer, Removal of solid cancers such as small intestine cancer, hepatocellular carcinoma, biliary tract cancer, stomach cancer, ovarian cancer, esophageal cancer, duodenal cancer, skin cancer, laryngeal cancer, pharyngeal cancer, oral cancer, uterine fibroid, ovarian cyst, lung tumor Removal of various tumors such as breast, colon, and brain tumors; removal of gallstones; removal of crushed tissue; lung resection due to lung infection; valve replacement, valvuloplasty, large vessel replacement, and chronic pulmonary thromboembolism Thrombus endarterectomy; removal of intracerebral hematoma; femoral head replacement; removal of an organ from a donor (organ donor), and the like.
本発明の一実施形態において、「器官または組織」として、これに限定されるものではないが、大血管、心臓（例えば弁又は心筋の一部）などの循環器系：食道、胃、十二指腸、小腸、大腸等の腸、脾臓、胆嚢、膵臓、肝臓などの消化器系；気管、肺などの呼吸器系；脳などの神経系；子宮、卵巣などの生殖器系；腎臓などの泌尿器；甲状腺、副甲状腺、下垂体、副腎、ランゲルハンス島、松果体などの内分泌系；眼、耳などの感覚器系；骨、筋などの運動器系；乳房；皮膚などを挙げることができる。上記器官または組織は、その一部であってもよいし、全部であってもよい。 In one embodiment of the invention, "organs or tissues" include, but are not limited to, the circulatory system, such as, but not limited to, the large blood vessels, the heart (eg, valves or parts of the heart muscle): Digestive system such as intestine such as small intestine and large intestine, spleen, gallbladder, pancreas and liver; respiratory system such as trachea and lungs; nervous system such as brain; genital system such as uterus and ovary; urinary system such as kidney; Examples include endocrine systems such as parathyroid gland, pituitary gland, adrenal gland, islet of Langerhans, and pineal gland; sensory systems such as eyes and ears; motor systems such as bones and muscles; breasts; The above-mentioned organ or tissue may be a part or the whole.
以下、本発明に係る器官または組織の摘出による体重減少を軽減するための医薬組成物（以下、本発明の医薬組成物とも称する）について説明する。 Hereinafter, a pharmaceutical composition (hereinafter, also referred to as the pharmaceutical composition of the present invention) for reducing weight loss due to the removal of an organ or tissue according to the present invention will be described.
本発明の医薬組成物は、水素ガスを含む気体状の医薬組成物であることを特徴とする。本発明において、水素原子は、その全ての同位体、すなわちプロチウム（Ｐまたは１Ｈ）、ジュウテリウム（Ｄまたは２Ｈ）、およびトリチウム（Ｔまたは３Ｈ）、のいずれであってもよい。したがって、分子状水素として、Ｐ2、ＰＤ、ＰＴ、ＤＴ、Ｄ2およびＴ2が含まれうる。本発明の好ましい態様において、本発明の医薬組成物に含まれる水素ガスの９９％以上は天然の分子状水素であるＰ２である。 The pharmaceutical composition of the present invention is a gaseous pharmaceutical composition containing hydrogen gas. In the present invention, the hydrogen atom may be any of its isotopes, namely, protium (P or 1 H), deuterium (D or 2 H), and tritium (T or 3 H). Thus, molecular hydrogen can include P 2 , PD, PT, DT, D 2 and T 2 . In a preferred embodiment of the present invention, 99% or more of the hydrogen gas contained in the pharmaceutical composition of the present invention are P 2 is a natural molecular hydrogen.
本発明の医薬組成物は、酸素ガスをさらに含むことができる。酸素ガスは、水素ガスと予め混合されて、混合ガスの形態で存在してもよいし、対象への投与直前にまたは投与時に、水素ガスと混合されてもよい。 The pharmaceutical composition of the present invention may further include oxygen gas. The oxygen gas may be pre-mixed with the hydrogen gas and exist in the form of a mixed gas, or may be mixed with the hydrogen gas immediately before or at the time of administration to the subject.
本発明の医薬組成物は、不活性ガスをさらに含むことができる。不活性ガスは、水素ガスまたは酸素ガスの防爆を目的として使用され、したがって、水素ガスおよび／または酸素ガスとの混合ガスの形態で存在し得る。本発明の医薬組成物に使用できる不活性ガスとしては、これに限定されるものではないが、窒素ガス、ヘリウムガス、アルゴンガスなどを使用することができる。本発明の一実施形態では、不活性ガスとして安価な窒素ガスが使用される。 The pharmaceutical composition of the present invention may further include an inert gas. The inert gas is used for the purpose of preventing the explosion of hydrogen gas or oxygen gas, and may therefore be present in the form of a gas mixture with hydrogen gas and / or oxygen gas. The inert gas that can be used in the pharmaceutical composition of the present invention is not limited to this, but nitrogen gas, helium gas, argon gas and the like can be used. In one embodiment of the present invention, inexpensive nitrogen gas is used as the inert gas.
本発明の医薬組成物において、水素ガスの濃度範囲は、これに限定されるものではないが、例えば１〜４％（ｖ／ｖ）とすることができる。水素ガス濃度の下限値は、器官または組織の摘出による体重減少を軽減する効果を発揮できる濃度の下限値として設定されるものである。したがって、摘出される器官または組織の種類等、摘出される範囲または量、摘出の原因となった疾患または症状などに応じて、摘出による体重減少を軽減することができる最小濃度を適宜設定することができる。一方、水素ガス濃度の上限値は、空気中における酸素の爆発限界が４％であるため、安全性の観点から設定されるものである。 In the pharmaceutical composition of the present invention, the concentration range of hydrogen gas is not limited to this, but can be, for example, 1 to 4% (v / v). The lower limit of the hydrogen gas concentration is set as the lower limit of the concentration at which the effect of reducing weight loss due to removal of an organ or tissue can be exerted. Therefore, the minimum concentration that can reduce weight loss due to extraction should be appropriately set according to the type or type of organ or tissue to be extracted, the range or amount to be extracted, the disease or symptom that caused the extraction, etc. Can be. On the other hand, the upper limit of the hydrogen gas concentration is set from the viewpoint of safety since the explosion limit of oxygen in the air is 4%.
本発明の医薬組成物において、酸素ガスの濃度は、水素ガス濃度が１〜４％（ｖ／ｖ）の前提のとき、２１％〜９９％（ｖ／ｖ）の範囲とすることができる。 In the pharmaceutical composition of the present invention, the oxygen gas concentration can be in the range of 21% to 99% (v / v) assuming that the hydrogen gas concentration is 1 to 4% (v / v).
本発明の医薬組成物において、不活性ガスの濃度は、水素ガスおよび／または酸素ガスの濃度を適切に維持し、かつ、これらのガスの防爆効果が得られる範囲で設定される。したがって、不活性ガスの濃度は、使用される水素ガスおよび／または酸素ガスの濃度に応じて、当業者は適宜適切な濃度を設定することができる。そのような不活性ガスの濃度は、例えば不活性ガスが窒素ガスの場合、例えば、０〜７８％（ｖ／ｖ）の範囲で任意にとり得る。 In the pharmaceutical composition of the present invention, the concentration of the inert gas is set within a range where the concentrations of the hydrogen gas and / or the oxygen gas are appropriately maintained and the explosion-proof effect of these gases is obtained. Therefore, those skilled in the art can appropriately set the concentration of the inert gas according to the concentration of the hydrogen gas and / or the oxygen gas used. The concentration of such an inert gas can be arbitrarily set, for example, in the range of 0 to 78% (v / v) when the inert gas is nitrogen gas.
なお、本明細書を通じて使用されるガスの濃度は、２０℃、１０１．３ｋＰａでの含有率を示すものとする。 Note that the concentration of gas used throughout the present specification indicates the content at 20 ° C. and 101.3 kPa.
本発明の医薬組成物において、水素ガスによる本発明の効果を損なわない限り、二酸化炭素などの他の大気中のガス、空気、または麻酔ガスなどをさらに含んでもよい。 The pharmaceutical composition of the present invention may further contain other atmospheric gas such as carbon dioxide, air, or anesthetic gas, as long as the effect of the present invention due to hydrogen gas is not impaired.
本発明の医薬組成物は、例えば吸引手段を用いた吸引により、対象に投与することができる。そのような吸引手段としては、これに限定されるものではないが、例えば吸引マスクを挙げることができる。吸引マスクは、対象への適切な濃度での投与が実現されるように、対象の口および鼻を同時に覆うものであることが好ましい。 The pharmaceutical composition of the present invention can be administered to a subject, for example, by suction using a suction means. Such a suction means is not limited to this, but includes, for example, a suction mask. Preferably, the suction mask simultaneously covers the mouth and nose of the subject so that administration at the appropriate concentration to the subject is achieved.
本発明の一実施形態において、本発明の医薬組成物は、対象にそのまま投与し得る形態で提供される。例えば、この実施形態では、本発明の医薬組成物は、水素ガスおよび不活性ガスのほか、呼吸のための酸素ガス、およびその他任意のガスを、適切な濃度で予め混合することによって調製された、混合ガスの形態で提供される。 In one embodiment of the present invention, the pharmaceutical composition of the present invention is provided in a form that can be directly administered to a subject. For example, in this embodiment, the pharmaceutical composition of the present invention was prepared by premixing hydrogen gas and an inert gas, oxygen gas for respiration, and any other gas at an appropriate concentration. , In the form of a gas mixture.
本発明の別の態様において、本発明の医薬組成物は、対象への投与直前または投与時に調製される形態で提供される。例えば、この実施形態では、本発明の医薬組成物は、水素ガスと不活性ガスとの混合ガスを収容した容器と、酸素ガスを収容した容器とが、配管を介して吸引マスクに接続され、対象への投与に適切な濃度となるような流量で吸引マウスに送り込まれることによって、提供される。本発明の一態様では、前記容器は、ガスボンベである。 In another aspect of the present invention, the pharmaceutical composition of the present invention is provided in a form prepared immediately before or at the time of administration to a subject. For example, in this embodiment, the pharmaceutical composition of the present invention, a container containing a mixed gas of hydrogen gas and an inert gas, and a container containing oxygen gas are connected to a suction mask via a pipe, It is provided by being delivered to the aspirated mouse at a flow rate that is appropriate for administration to the subject. In one aspect of the present invention, the container is a gas cylinder.
本発明の別の態様において、本発明の医薬組成物は、ガスの濃度が一定に維持されるように、密閉小室に水素ガスを供給することによって提供される。例えば、この実施形態では、本発明の医薬組成物は、対象が存在する密閉小室に、前記密閉小室中の水素濃度が適切な濃度に維持されるような流量で、水素ガスと不活性ガスとからなる混合ガスを供給することによって提供される。 In another aspect of the present invention, the pharmaceutical composition of the present invention is provided by supplying hydrogen gas to a closed cell so that the concentration of the gas is kept constant. For example, in this embodiment, the pharmaceutical composition of the present invention may contain hydrogen gas and an inert gas at a flow rate such that the hydrogen concentration in the closed cell is maintained at an appropriate concentration in the closed cell in which the object is present. By supplying a mixed gas consisting of
本発明の医薬組成物は、ガスを収容する１個または複数個の容器の形態、またはガスを収容する複数の容器と、ガスを吸入するための吸入手段と、前記複数の容器とガス吸入手段とを接続する配管とを含む、ガス吸入用デバイスの形態で提供され得る。本発明の一実施形態において、ガス吸入用デバイスは、ガスを収容する各容器からのガス吸入手段へのガスの流量を制御する制御機構を備えることが好ましい。 The pharmaceutical composition of the present invention may be in the form of one or more containers containing gas, or a plurality of containers containing gas, inhalation means for inhaling gas, the plurality of containers and gas inhalation means And a pipe connecting the gas supply device and the gas supply device. In one embodiment of the present invention, the gas suction device preferably includes a control mechanism for controlling the flow rate of gas from each container containing gas to the gas suction means.
本発明の医薬組成物の対象への投与は、手術前、手術中または手術後のいずれの時点で開始することができ、また、手術前、手術中、または手術後のいずれか、または全ての時点で投与することができる。 Administration of the pharmaceutical composition of the present invention to a subject can begin at any time before, during, or after surgery, and can be performed before, during, or after surgery, or all. It can be administered at the time.
本発明の医薬組成物の投与間隔および投与回数は、対象の症状、体重減少の早さ、その他対象の年齢および性別などに応じて、当業者が、適宜適切な投与間隔および投与回数を設定することができる。本発明の一実施形態では、本発明の医薬組成物は、手術後一定の期間にわたって、複数回投与される。例えば、本発明の医薬組成物は、手術後少なくとも１日以上、好ましくは少なくとも５日以上、より好ましくは少なくとも１０日以上、より好ましくは少なくとも１５日以上、より好ましくは少なくとも２０日以上、より好ましくは少なくとも２５日以上、より好ましくは少なくとも３０日以上、連日投与される。手術後、体重の減少が増加に転じるまで吸入させることが好ましい。 The administration interval and the number of administrations of the pharmaceutical composition of the present invention are appropriately set by a person skilled in the art according to the condition of the subject, the speed of weight loss, the age and sex of the subject, and the like, and appropriately set the administration interval and the number of administrations. be able to. In one embodiment of the invention, the pharmaceutical composition of the invention is administered multiple times over a period of time after surgery. For example, the pharmaceutical composition of the present invention is preferably at least 1 day or more, preferably at least 5 days or more, more preferably at least 10 days or more, more preferably at least 15 days or more, more preferably at least 20 days or more, more preferably after surgery. Is administered daily for at least 25 days or more, more preferably at least 30 days or more. After surgery, it is preferable to inhale until weight loss starts to increase.
本発明の医薬組成物の一回あたりの投与時間は、対象の症状、体重減少の早さ、その他対象の年齢および性別などに応じて、当業者が、適宜適切な投与間隔および投与回数を設定することができる。例えば、本発明の医薬組成物の一回あたりの投与時間は、１日あたり、０．１時間〜２４時間、好ましくは０．５時間〜１２時間、より好ましくは０．５時間〜１２時間、より好ましくは０．５時間〜６時間、より好ましくは０．５時間〜３時間、例えば１時間とすることができる。 The administration time per administration of the pharmaceutical composition of the present invention is appropriately set by the person skilled in the art according to the symptoms of the subject, the speed of weight loss, the age and sex of the subject, etc. can do. For example, the administration time per dose of the pharmaceutical composition of the present invention is 0.1 hour to 24 hours, preferably 0.5 hour to 12 hours, more preferably 0.5 hour to 12 hours per day. More preferably, it can be set to 0.5 to 6 hours, more preferably 0.5 to 3 hours, for example, 1 hour.
本発明の医薬組成物の投与対象は、特に限定されないが、典型的にはヒトである。 The subject to which the pharmaceutical composition of the present invention is administered is not particularly limited, but is typically a human.
本発明の医薬組成物によれば、水素ガスを投与しない場合との比較において、器官または組織の摘出後の最大体重減少を、１０％以上、好ましくは２０％以上、より好ましくは３０％以上、より好ましくは４０％以上、より好ましくは５０％以上、より好ましくは６０％以上、より好ましくは７０％以上、より好ましくは８０％以上、そして最も好ましくは９０％以上軽減することができる。 According to the pharmaceutical composition of the present invention, the maximum weight loss after extirpation of an organ or tissue is 10% or more, preferably 20% or more, more preferably 30% or more, as compared with the case where hydrogen gas is not administered. More preferably, it can be reduced by 40% or more, more preferably 50% or more, more preferably 60% or more, more preferably 70% or more, more preferably 80% or more, and most preferably 90% or more.
あるいは、本発明の医薬組成物によれば、水素ガスを投与しない場合との比較において、器官または組織の摘出後の体重減少を、少なくとも２０％以下、好ましくは１５％以下、より好ましくは１０％以下、より好ましくは９％以下、より好ましくは８％以下、より好ましくは７％以下、より好ましくは６％以下、そして最も好ましくは５％以下に抑制することができる。 Alternatively, according to the pharmaceutical composition of the present invention, the weight loss after extirpation of an organ or a tissue is reduced by at least 20% or less, preferably 15% or less, more preferably 10% or less as compared with the case where hydrogen gas is not administered. Or less, more preferably 9% or less, more preferably 8% or less, more preferably 7% or less, more preferably 6% or less, and most preferably 5% or less.
本明細書において用いられる用語は、特定の実施態様を説明するために用いられるのであり、発明を限定する意図ではない。 The terms used in the specification are used to describe the specific embodiment and are not intended to limit the invention.
また、本明細書において用いられる「含む」との用語は、文脈上明らかに異なる理解をすべき場合を除き、記載された事項（部材、ステップ、要素または数字等）が存在することを意図するものであり、それ以外の事項（部材、ステップ、要素または数字等）が存在することを排除しない。 Further, the term “comprising”, as used herein, is intended to include the stated matter (eg, member, step, element or number), unless context clearly requires a different understanding. And does not exclude the existence of other items (members, steps, elements, numbers, etc.).
本明細書中に引用される文献は、それらのすべての開示が、本明細書中に援用されているとみなされるべきであって、当業者は、本明細書の文脈に従って、本発明の精神および範囲を逸脱することなく、それらの先行技術文献における関連する開示内容を、本明細書の一部として援用することができる。 The documents cited herein are to be considered as having their entire disclosures incorporated herein, and those skilled in the art, in accordance with the context of this specification, Without departing from the scope, the relevant disclosures in those prior art documents can be incorporated as part of the present specification.
以下、実施例を示して本発明をより具体的に説明するが、本発明は以下に示す実施例によって何ら限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples.
ラット５／６腎摘モデルを作製し、水素混合ガス環境下での術後の経過を観察し、体重減少への影響を評価した。 A rat 5/6 nephrectomy model was prepared, the postoperative course was observed in a hydrogen-mixed gas environment, and the effect on weight loss was evaluated.
ラット５／６腎摘モデルの作製には、１０週齢のＬｅｗｉｓラット（雄）を用いた。ラット５／６腎摘モデルは、ラットを、イソフルランを用いた笑気吸入麻酔下におき、以下の外科的処置を施すことによって作製した。すなわち、腹部を正中切開し、右腎を露出し、右腎を周囲脂肪織より剥離した後、腎門部で腎動静脈・尿管を結紮切離、右腎を摘出した。次いで、左腎を露出し、腎臓を周囲脂肪織より剥離した後、上下腎動脈分枝を結紮した。なお、コントロール群は、開腹後、両腎の脂肪織からの剥離のみを行い、体重変化のみを調査した。 For the preparation of a rat 5/6 nephrectomy model, a 10-week-old Lewis rat (male) was used. The rat 5/6 nephrectomy model was prepared by placing a rat under laughter inhalation anesthesia using isoflurane and performing the following surgical procedure. That is, a midline incision was made in the abdomen, the right kidney was exposed, and the right kidney was exfoliated from the surrounding fat tissue. Next, after exposing the left kidney and exfoliating the kidney from the surrounding fatty tissue, the upper and lower renal artery branches were ligated. In addition, in the control group, after laparotomy, only exfoliation of both kidneys from fat tissue was performed, and only the change in body weight was investigated.
上記処置を行った各ラットは、術後当日、麻酔から完全に覚醒した段階で、ラット用ケース内に維持し、ガス吸入試験に供した。ラットを水素群（窒素＋１．３％水素＋２６％酸素、Ｎ＝３）、窒素群（窒素＋２６％酸素、Ｎ＝３）の２群に分け、ラット用ケース内で１時間ずつ各ガスを吸入させた。吸入は、前記組成の水素混合ガスまたは窒素ガスを、ラット用ケース内に一定の流量で供給することにより行った。なお、ラット用ケース内の水素濃度が均一に維持されていることは、吸引式ガス濃度計でモニタリングすることにより確認した。 On the day after the operation, each of the rats subjected to the above treatment was completely awakened from anesthesia, maintained in a rat case, and subjected to a gas inhalation test. Rats are divided into two groups, a hydrogen group (nitrogen + 1.3% hydrogen + 26% oxygen, N = 3) and a nitrogen group (nitrogen + 26% oxygen, N = 3), and each gas is inhaled for 1 hour in a rat case. I let it. The inhalation was performed by supplying a hydrogen mixed gas or a nitrogen gas having the above composition at a constant flow rate into a rat case. In addition, it was confirmed by monitoring with a suction type gas concentration meter that the hydrogen concentration in the rat case was maintained uniformly.
水素吸入は、１時間／日のスケジュールで、術後２８日目まで連日行い、その間、術後２８日までの体重を測定した（図１）。 Hydrogen inhalation was performed on a daily schedule until the 28th day after the operation on a 1 hour / day schedule, during which time the body weight was measured until the 28th day after the operation (FIG. 1).
水素群および窒素群ともに手術直後に急激な体重減少を示したが、水素群では術後２日に減少のピークを迎え、術後３日目には体重増加に転じたのに対し、窒素群では術後７日まで体重減少が続き、体重増加に転じたのは術後９日目であった。また、窒素群では、最大体重減少が、ラット全体重のおよそ１８％に達したのに対し、水素群では、ラット全体重のおよそ７．５％に留まった。２−３日の間に２０％以上の体重減少、もしくは、７日間で２５％以上の体重減少が認められる動物は、安楽死の対象にするべきとの倫理基準もあることから、水素群の動物は、安楽死を十分に免れるレベルにまで体重減少を抑制できたという点で、極めて驚くべき結果であった。またこの結果は、水素ガスの吸入によって、吸入を行わなかった群に比較して、ラットの体重減少がおよそ６０％近くも軽減されたことを示している。 Both the hydrogen group and the nitrogen group showed a rapid loss of body weight immediately after surgery, but the hydrogen group peaked on the 2nd postoperative day and turned to weight gain on the 3rd postoperative day. In this case, weight loss continued until 7 days after the operation, and it turned to weight gain on the 9th day after the operation. In the nitrogen group, the maximum body weight loss reached approximately 18% of the total weight of the rat, whereas in the hydrogen group, it decreased to approximately 7.5% of the total weight of the rat. Animals with a weight loss of 20% or more in 2-3 days or 25% or more in 7 days are subject to euthanasia. The results were extremely surprising in that the animals were able to control their weight loss to a level that was well under euthanasia. The results also show that inhalation of hydrogen gas reduced the weight loss of rats by nearly 60% compared to the group without inhalation.
本発明の医薬組成物によれば、器官または組織の摘出による体重減少を軽減することができる。
ADVANTAGE OF THE INVENTION According to the pharmaceutical composition of this invention, weight loss by excision of an organ or a tissue can be reduced.
Claims (13)
器官または組織の摘出による体重減少を軽減するための、
医薬組成物。 A gaseous pharmaceutical composition comprising hydrogen gas,
To reduce weight loss due to removal of organs or tissues,
Pharmaceutical composition.
酸素ガスをさらに含むことを特徴とする、
医薬組成物。 A pharmaceutical composition according to claim 1,
Characterized by further containing oxygen gas,
Pharmaceutical composition.
不活性ガスをさらに含むことを特徴とする、
医薬組成物。 The composition according to claim 1 or 2, wherein
Characterized by further comprising an inert gas,
Pharmaceutical composition.
前記水素ガスの濃度が、１〜４％（ｖ／ｖ）である
ことを特徴とする、
医薬組成物。 It is a pharmaceutical composition according to any one of claims 1 to 3,
The concentration of the hydrogen gas is 1 to 4% (v / v).
Pharmaceutical composition.
前記水素ガスの濃度が、１〜４％（ｖ／ｖ）であり、
前記酸素ガス濃度が２１〜９９％（ｖ／ｖ）である
ことを特徴とする、
医薬組成物。 A pharmaceutical composition according to any one of claims 2 or 3, wherein
A concentration of the hydrogen gas is 1 to 4% (v / v);
The oxygen gas concentration is 21 to 99% (v / v),
Pharmaceutical composition.
１日あたり０．５〜２４時間投与される
ことを特徴とする、
医薬組成物。 It is a pharmaceutical composition according to any one of claims 1 to 5,
Characterized in that it is administered for 0.5 to 24 hours per day,
Pharmaceutical composition.
手術日後少なくとも１日以上投与される
ことを特徴とする、
医薬組成物。 A pharmaceutical composition according to any one of claims 1 to 6,
Characterized by being administered at least one day after the operation day,
Pharmaceutical composition.
手術前、および／または、手術中において投与される
ことを特徴とする、
医薬組成物。 A pharmaceutical composition according to any one of claims 1 to 7,
Characterized in that it is administered before surgery and / or during surgery.
Pharmaceutical composition.
前記「器官または組織の摘出」が癌、腫瘍、胆石、挫滅した組織の摘出；肺感染症による肺切除；弁置換、弁形成、大血管置換術、慢性肺血栓塞栓症に対する血栓内膜剥皮術；脳内血腫の除去；大腿骨頭置換術；またはドナーからの臓器摘出に伴う
ことを特徴とする、
医薬組成物。 It is a pharmaceutical composition according to any one of claims 1 to 8,
Removal of cancer, tumor, gallstones, or crushed tissue; removal of lungs due to pulmonary infection; valve replacement, valvuloplasty, large vessel replacement, thrombus intimal stripping for chronic pulmonary thromboembolism Removal of intracerebral hematoma; femoral head replacement; or with removal of an organ from a donor;
Pharmaceutical composition.
前記「器官または組織」が、循環器系：消化器系；呼吸器系；神経系；生殖器系；泌尿器；内分泌系；感覚器系；運動器系；乳房；または皮膚からなる群から選ばれる器官または組織の全部または一部である
ことを特徴とする、
医薬組成物。 It is a pharmaceutical composition according to any one of claims 1 to 9,
Said organ or tissue is an organ selected from the group consisting of circulatory system: digestive system; respiratory system; nervous system; reproductive system; urinary system; endocrine system; sensory system; Or being all or part of an organization,
Pharmaceutical composition.
前記「器官または組織」が、大血管、心臓、食道、胃、十二指腸、小腸、大腸、脾臓、胆嚢、膵臓、肝臓、気管、肺、脳、子宮、卵巣、腎臓、甲状腺、副甲状腺、下垂体、副腎、ランゲルハンス島、松果体、眼、耳、骨、筋肉、乳房、および皮膚からなる群から選ばれる器官または組織の全部または一部である
ことを特徴とする、
医薬組成物。 It is a pharmaceutical composition according to any one of claims 1 to 9,
The `` organ or tissue '' is a large blood vessel, heart, esophagus, stomach, duodenum, small intestine, large intestine, spleen, gallbladder, pancreas, liver, trachea, lung, brain, uterus, ovary, kidney, thyroid, parathyroid, pituitary gland , Adrenal gland, islet of Langerhans, pineal gland, eye, ear, bone, muscle, breast, and all or a part of an organ or tissue selected from the group consisting of skin,
Pharmaceutical composition.
水素ガスを投与しない場合との比較において、器官または組織の摘出後の最大体重減少を、３０％以上軽減することを特徴とする、
医薬組成物。 It is a pharmaceutical composition according to any one of claims 1 to 11,
The method is characterized in that the maximum body weight loss after removal of an organ or tissue is reduced by 30% or more as compared with the case where hydrogen gas is not administered.
Pharmaceutical composition.
器官または組織の摘出による体重減少は、全体重の少なくとも１０％または少なくとも１５％の減少である、Weight loss due to removal of an organ or tissue is a reduction of at least 10% or at least 15% of total body weight;
医薬組成物。Pharmaceutical composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015213481A JP6630115B2 (en) | 2015-10-29 | 2015-10-29 | Pharmaceutical composition for reducing weight loss after extirpative surgery |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015213481A JP6630115B2 (en) | 2015-10-29 | 2015-10-29 | Pharmaceutical composition for reducing weight loss after extirpative surgery |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017081862A JP2017081862A (en) | 2017-05-18 |
| JP6630115B2 true JP6630115B2 (en) | 2020-01-15 |
Family
ID=58712755
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015213481A Active JP6630115B2 (en) | 2015-10-29 | 2015-10-29 | Pharmaceutical composition for reducing weight loss after extirpative surgery |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6630115B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021109860A (en) * | 2020-01-15 | 2021-08-02 | ＭｉＺ株式会社 | Molecular hydrogen-containing composition for promotion of postoperative recovery |
| JP7019910B2 (en) * | 2020-07-21 | 2022-02-16 | ＭｉＺ株式会社 | Compositions for preventing and / or ameliorating side effects of a drug, symptoms associated with the side effects of a drug, and / or side effects associated with treatment. |
-
2015
- 2015-10-29 JP JP2015213481A patent/JP6630115B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2017081862A (en) | 2017-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2554108T3 (en) | Methods of treatment of necrotizing enterocolitis | |
| JP6630115B2 (en) | Pharmaceutical composition for reducing weight loss after extirpative surgery | |
| JP2022159439A (en) | Molecular hydrogen-containing composition for promotion of postoperative recovery | |
| AU2004283448B2 (en) | Use of xenon for the prevention of programmed cell death | |
| Monnier | Partial cricotracheal resection | |
| Dolan et al. | Anaesthesia for tracheobronchial stent insertion using an laryngeal mask airway and high-frequency jet ventilation | |
| Winge et al. | VAC® for external fixation of flail chest | |
| JP7414202B2 (en) | Molecular hydrogen-containing composition for maintaining lung function during human lung cancer and/or improving lung function decline caused by human lung cancer | |
| Cotton et al. | Intratracheal insufflation anaesthesia: considered from its physiological and clinical aspects | |
| JP2022049676A (en) | Composition containing molecular hydrogen for preventing and/or improving chronic inflammation | |
| FR3007653A3 (en) | USE OF NOBLE GAS FOR THE TREATMENT OF INTESTINAL REPERFUSION ISCHEMAS | |
| Clover | Laryngotomy in chloroform asphyxia | |
| Hardjo et al. | Exploring through the difficulties: Fiber optic laryngoscope in ameloblastoma patient | |
| Emery et al. | 2 Inhalation Anesthetic Agents | |
| Richard et al. | Pressure versus volume assist-control ventilation in Acute Respiratory Distress Syndrome: a randomised clinical trial. | |
| Castro et al. | Supracricoid laryngectomy | |
| Prisman et al. | A novel endoscopically placed stent to relieve glottic obstruction from bilateral vocal fold paralysis | |
| JP2014141536A (en) | Therapeutic agent and therapeutic device for ischemia-reperfusion injury alleviation | |
| Dillard | Ethylene—The New General Anesthetic | |
| RU2297851C1 (en) | Method for correcting respiratory disorders when carrying out patient sedation under spinal anesthesia | |
| Williams | Management of tracheal collapse. | |
| Cartwright | Vinesthene Mixture | |
| Bier | Danger Signals in Nitrous Oxide Oxygen Anaesthesia | |
| Dundas-Grant | Laryngeal Obstruction in a Man Suffering from Lymphatic Leukæmia (Specimen) | |
| Warwick | Plastic surgery |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180823 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190723 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190903 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191112 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20191206 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6630115 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |