WO2007055044A1 - 麻酔覚醒促進剤 - Google Patents
麻酔覚醒促進剤 Download PDFInfo
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- WO2007055044A1 WO2007055044A1 PCT/JP2006/310671 JP2006310671W WO2007055044A1 WO 2007055044 A1 WO2007055044 A1 WO 2007055044A1 JP 2006310671 W JP2006310671 W JP 2006310671W WO 2007055044 A1 WO2007055044 A1 WO 2007055044A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to an anesthetic wake-promoting agent that promotes wakefulness from anesthesia, and more particularly to an anesthetic-wakefulness promoting agent that promotes wakefulness from anesthesia during a perioperative period. Furthermore, the present invention relates to a method for managing * promoting arousal from anesthesia by administering the arousal promoting agent. Furthermore, the present invention relates to an acidosis correcting agent, and also relates to a method for managing and promoting arousal from anesthesia while maintaining blood pH at a value close to a normal value.
- anesthesia during surgery in this case can be broadly divided into general anesthesia and local anesthesia.
- General anesthesia is performed during relatively large and complicated procedures, and general anesthesia includes inhalation anesthesia (gas anesthesia) and venous anesthesia.
- inhalation anesthesia inhalation anesthesia
- inhalation anesthetics such as ether, halothane, elflurane, isoflurane, methoxyflurane and sevoflurane are used.
- Inhalation anesthesia has the great advantage that it is generally vaporized, absorbed immediately from the lungs and excreted from the lungs, and is characterized by rapid introduction of anesthesia and awakening from anesthesia.
- inhalation anesthesia gas anesthesia
- intravenous anesthetics such as pentobarbital, thiopental, methoxyhetal, and provophor are used for intravenous anesthesia.
- Intravenous anesthetics are characterized by rapidly reaching the target organ (brain) by intravenous injection and losing consciousness.
- There are various types such as short-acting and long-acting, depending on the type.
- provophor a continuous-use intravenous anesthetic, is the mainstream in Japan, with 1% Dupriban Injection (AstraZeneca), 1% Provophor Injection (Maruishi Pharmaceutical), etc. being promoted .
- Patent Document 1 JP 2004-149495 A
- the present invention provides a method for promoting awakening without depending on the experience of an anesthesiologist for postoperative anesthesia, and an arousal promoting agent from anesthesia used therefor The task is to do.
- arousal promoting agent from anesthesia used therefor The task is to do.
- the present invention has the following configuration as an aspect thereof.
- Anesthesia wake-promoting agent characterized by containing bicarbonate ion
- Anesthesia as described in (1) or (2) above characterized by comprising sodium bicarbonate as a bicarbonate ion as a main component, and further using other electrolytes, glucose, and amino acids alone or in combination.
- Arousal promoter characterized by comprising sodium bicarbonate as a bicarbonate ion as a main component, and further using other electrolytes, glucose, and amino acids alone or in combination.
- the present invention provides:
- the present invention provides, as another aspect,
- An anesthesia wake-promoting agent according to any one of (1) to (8) above, Or a method of managing and promoting arousal from anesthesia characterized by administering an acidosis corrector;
- the anesthesia wake-promoting agent provided by the present invention basically contains bicarbonate ions, and more specifically, sodium bicarbonate that becomes bicarbonate ions as an electrolyte is the main component. It is an infusion solution that can promote early arousal from general anesthesia after surgery.
- an infusion solution containing sodium bicarbonate, which is a bicarbonate ion, as a main component as an electrolyte provided by the present invention quickly corrects acidosis and maintains blood pH at a normal value or a value close to a normal value. This increases the protein binding rate of the anesthetic administered by this method, which can promote early awakening from postoperative general anesthesia.
- FIG. 1 is a diagram showing the results of Example 6.
- Anesthesia wake-promoting agent or acidosis corrector (hereinafter simply referred to as anesthesia wake-promoting agent) provided by the present invention contains a bicarbonate ion having an action of promoting wake-up from anesthesia as described above. It is characterized by that. More specifically, the main component is sodium bicarbonate (sodium bicarbonate) as a bicarbonate ion, and other electrolytes, glucose, A preparation containing a single amino acid or a combination of a plurality of amino acids, preferably an infusion solution, an anesthesia wake-promoting agent in the form of Ringer's solution, maintenance solution, starter solution, dehydration correction solution or postoperative recovery solution, particularly Ringer's solution An anesthesia-wake promoting agent in the form of
- the anesthetic / wakefulness-promoting agent containing bicarbonate ions provided in the present invention is in the form of a Ringer's solution formulation as an extracellular fluid replenisher
- the bicarbonate ion concentration is 20 to 40 mEq / L, more preferably an infusion containing 22-30mEqZL.
- the bicarbonate ion concentration is 15 to 30 mEq / L, more preferably 18 to 25 mE q / L. It is a blended infusion solution, and at the same time, as other electrolytes, sodium ions 30 to 40 mEq / L, potassium ions 15 to 25 mEq / L, chloride ions 30 to 40 mEq / L, and glucose 40 to 80 g / L is preferable.
- Masle sodium ions 30 to 40 mEq / L, potassium ions 15 to 25 mEq / L, chloride ions 30 to 40 mEq / L, and glucose 40 to 80 g / L is preferable.
- the anesthetic wake-promoting agent containing bicarbonate ions provided in the present invention is in the form of an initiating solution, a dehydration correction solution, or a postoperative recovery solution, the target bicarbonate ion concentration and Various electrolyte components are blended.
- sodium ions 30 to 90mEq / L may contain sodium ions 30 to 90mEq / L, chlorine ions 35 to 80mEq / L, bicarbonate ions 20 to 30mEqZL, and glucose 25 to 40g / L. desirable.
- sodium ions 60 to 90 mEq / L sodium ions 60 to 90 mEq / L, potassium ions 20 to 30 mEqZL, magnesium ions 0 to 5 mEq / L, chlorine ions 45 to 70 mEq / L, phosphorus 5 to 10 mmol ZL, bicarbonate ions 20 to It is desirable to contain 50mEq / L and glucose 10-35gZL.
- electrolyte components can be used without particular limitation, if necessary.
- Particularly preferable components are sodium chloride sodium, potassium salt potassium, calcium chloride, sodium magnesium salt, sodium hydrogen carbonate, sodium citrate, glucose and the like.
- sodium bicarbonate which is a source of bicarbonate ions, which is an important base for controlling acid-base balance of extracellular fluid, It reacts with calcium and magnesium to precipitate insoluble calcium carbonate and magnesium carbonate, and has the property of raising the pH by releasing carbon dioxide when the aqueous sodium hydrogen carbonate solution is left or heated. From the above, it was difficult to obtain a stable sodium bicarbonate ion-containing preparation in terms of preparation.
- the infusion solution containing bicarbonate ions of the present invention may be prepared at the time of use, or a combination of two agents of a sodium hydrogen carbonate solution and an electrolyte solution, or a preparation filled with these in a two-chamber container.
- the transfusion as an anesthesia and wake-promoting agent containing bicarbonate ion provided by the present invention is stable in terms of formulation, and is administered to a patient during the perioperative period, thereby transfusion containing other acetic acid. It promotes early arousal from general anesthesia compared to infusions containing lactic acid and lactic acid.
- the transfusion as an anesthetic wake-promoting agent containing bicarbonate ion provided by the present invention is preferably administered to a perioperative anesthetized patient, that is, administered as a perioperative transfusion. Promotes awakening from.
- perioperative infusions when administered as Ringer's solution, specifically, it is used as follows.
- the present invention manages and promotes anesthesia from anesthesia by administering the anesthesia arousal promoter of the present invention to a perioperative anesthetized patient. It becomes possible to make it.
- raising the low blood pH increases the protein binding rate of anesthetics and accelerates wakefulness from anesthesia.
- the anesthetic wakefulness-promoting agent of the present invention has an excellent acidosis correction effect, and thus maintains the blood pH at a normal value or a value close to the normal value. As a result, wakefulness from anesthesia is accelerated.
- Ringer's solution as an anesthesia wake-promoting agent containing bicarbonate ion of the present invention significantly accelerates wakefulness in a rat partial hepatectomy model compared to lactated Ringer, and in an STZ-induced ureteric ketoacidosis model Significantly awakened compared to Ringer acetate.
- sodium bicarbonate can supply bicarbonate ions without interfering with metabolism, so it can exert an alkalizing effect even in the presence of metabolic disorders and organ disorders.
- the blood pH can be maintained at a high value as compared with the case where Ringer's solution is used. Therefore, the anesthetic / wakefulness-promoting agent of the present invention promotes awakening from anesthesia after the end of anesthesia by being administered during the perioperative period (during surgery).
- an infusion preparation was prepared according to the formulation described in Table 1 below.
- Each compounding component was dissolved in water to 10 L (pH measured value: 8.0), adjusted to pH 6.5 by bubbling carbon dioxide, then filtered and filled into a 500 mL glass vial. This was autoclaved at 115 ° C for 15 minutes, so that the bicarbonate ion (HCO-) concentration was 20. 0 22. 5 25. 0 27.
- Example 2 Examination of f: awakening time using rat partial hepatectomy model (short-time operation)
- Ringer's solution as an anesthetic wake-promoting agent containing the bicarbonate ion of the present invention consisting of the formulation shown in Table 4 below at 20 mLZKg / hour from a 7-week-old SD male rat placed in a right vein.
- Administration was started, and provophor, an intravenous anesthetic, was continuously administered at 45 mgZkg / hour 30 minutes after the start of administration.
- provophor an intravenous anesthetic
- the time from the end of anesthesia administration to awakening was compared in each administration group.
- the definition of arousal was defined as the time when the rat's normal reflex was restored and he was able to walk.
- Ringer's solution administration group of the present invention 29 cases
- Lactated Ringer's solution administration group 19 cases.
- the administration group of Ringer's solution as an infusion solution that is an anesthesia wake-promoting agent of the present invention has a significantly faster time to wake-up than the Lactated Ringer's solution administration group. Yes (p ⁇ 0. 05), and the awakening time tended to be faster compared to the group treated with Ringer acetate ((p ⁇ 0.06)). Therefore, the characteristics of the arousal promoting effect from anesthesia possessed by the anesthesia awakening promoter of the present invention can be well understood.
- Example 3 Examination of f: arousal rate using rat partial hepatectomy model (long-term operation)
- Ringer's solution as an anesthetic wake-promoting agent containing the bicarbonate ion of the present invention consisting of the formulation shown in Table 4 above was injected into a 7-week-old SD male rat from a catheter placed in the right venous vein at 20 mLZKg / hr.
- Provofor, a intravenous anesthetic was continuously administered at 45 mg / kg / hour.
- the abdomen of the rat was opened, and about 30% of the liver (left and right outer lobes and left inner lobe) was excised 30 minutes after laparotomy, and the abdomen was closed 60 minutes after the laparotomy. finished.
- Ringer's solution and anesthesia were administered for a total of 90 minutes from the end of surgery to 30 minutes, and the time from the end of anesthesia administration until waking up was compared for each administration group.
- the definition of arousal was defined as the point when the rat's normal reflex was restored and he was able to walk.
- Ringer's solution administration group of the present invention 38 cases
- Lactated Ringer's solution administration group 18 cases.
- Table 6 summarizes the arousal rate and average arousal time at 2 hours, 3 hours, and 4 hours after the end of anesthesia for each administration group.
- the Ringer's solution administration group of the present invention had a shorter awakening time than the lactate Ringer's solution administration group (p ⁇ 0. 05).
- Example 4 Study of translocation of blood anesthetic concentration using rat partial hepatectomy model
- SD male rats (7 rats per group) fasted for about 16 hours from the day before the test contain the bicarbonate ion of the present invention consisting of the formulation described in Table 4 above from a catheter inserted by central vein placement.
- Administration of Ringer's solution as an anesthetic wake-promoting agent was started at 20 mL / Kg / hour. From 30 minutes after the start of administration, Provofol (1% dupliban injection) was administered at 45 mg / kg / hour, and the abdomen of the rat was opened, and 15 minutes after the start of anesthetic administration At that time, approximately 75% of the liver was excised and closed 30 minutes after laparotomy. The drug was administered for 30 minutes during the operation, and Ringer's solution was administered for a total of 90 minutes until 30 minutes after the end of the anesthetic administration.
- an acetate ringer solution or a lactate ringer solution having the formulation described in Table 4 above was used and tested in the same manner.
- Table 7 (Ringer solution of the present invention), Table 8 (Ringer acetate solution), and Table 9 (Lactated Ringer solution) show the transition of plasma anesthetic (Provophor) in each group.
- the plasma anesthetic (provophor) concentration showed the highest value immediately before the end of anesthetic administration (30 minutes after the start of administration) in each administration group, and gradually thereafter. Declined. There was no significant difference between the groups, but the plasma anesthetic concentration in the Lactated Ringer's solution administration group was determined at the end of anesthesia administration, 60 minutes after the end of anesthesia administration, and 90 minutes after the end of anesthesia administration. It was a high price trend.
- Example 5 Effect of sputum on the binding of provophor to human serum albumin
- 50 mM phosphate buffer was prepared and adjusted to pH 7.0, 7.2, 7.4, 7, 6 and 7.8, respectively, so that human serum albumin (hereinafter referred to as 40 mg / mL) was obtained. HAB) was added.
- the ratio of free provophor shows a higher value as the pH of the solution is lower, and this indicates that the protein binding rate of provophor changes due to fluctuations in blood pH, and the percentage of free form increases as it becomes acidic. It was suggested to do. This suggests that even if the total provophor concentration is the same, in the acidosis state, the proportion of free provophor is higher than in the normal state, and the anesthetic action may be enhanced.
- Example 6 Study on the relationship between acidosis and arousal time using streptozotocin (STZ) -induced rat diabetic ketoacidosis model (Part 1)
- STZ was dissolved in 1 M citrate buffer to prepare an STZ aqueous solution, which was administered to rats via the tail vein at 100 mg / kg / mL. Blood gas at 48 hours after administration was measured to confirm the occurrence of acidosis.
- the Japanese Pharmacopoeia Ringer's solution was administered as a test infusion solution through a catheter inserted by central vein placement for 90 minutes at 20 mLZkgZ time.
- provophor 1% dupliban injection
- a intravenous anesthetic was administered for 90 minutes. The time from the end of administration to awakening was measured.
- Figure 1 shows the relationship between blood pH and time required for awakening.
- Example 7 Study on waking time using STZ-induced rat diabetic ketoacidosis model (Part 2) —Comparison between the present invention and Ringer acetate
- Ringer's solution the bicarbonate Ringer's solution, acetate Ringer's solution, or Japanese Pharmacopoeia Ringer's solution (hereinafter referred to as Ringer's solution) of the present invention is administered as a test infusion solution through a catheter inserted by central vein placement for 90 minutes at 20 mL / kgZ time, and at the same time, a vein anesthetic Provophor (1% dupliban injection) was also administered for 90 minutes. The time from the end of administration to awakening was measured.
- Bicarbonate Ringer group of the present invention 33.7 ⁇ 21.5 minutes
- the bicarbonate Ringer group of the present invention was the most awakened from anesthesia, and the Ringer group and Ringer group were almost equivalent.
- the awakening time of the bicarbonate Ringer group of the present invention was significantly earlier than that of the acetate Ringer group (p ⁇ 0.05). Based on the above results, diabetic ketoacidosis produces a large amount of ketone bodies in the body, and the metabolism of ketone bodies antagonizes the metabolism of acetic acid. This was considered to have affected the awakening time because the acidosis correction effect was not sufficiently obtained.
- the present invention provides Ringer's solution containing bicarbonate ions among extracellular fluid replenishers (Ringer's solution) that are replenished as a substitute for blood for patients in the perioperative period (in operation). Is used to correct acidosis and promote early awakening from anesthesia, and the stability of the infusion is good.By promoting early awakening, recovery of metabolic function is achieved, Recovery of spontaneous breathing and maintenance of the function of tissues' organs can be carried out at an early stage, thereby avoiding the risk of causing complications due to delays in the body's defense response and decreased immunity.
- Ringer's solution containing bicarbonate ions among extracellular fluid replenishers (Ringer's solution) that are replenished as a substitute for blood for patients in the perioperative period (in operation). Is used to correct acidosis and promote early awakening from anesthesia, and the stability of the infusion is good.By promoting early awakening, recovery of metabolic function is achieved, Recovery of spontaneous breathing and maintenance of the function of tissues' organs can be carried out at an early stage,
- the patient's care at the ICU due to the patient's delay in awakening can be reduced, and the work amount of the staff at the medical site can be reduced. Is.
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Abstract
Description
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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KR1020087013756A KR101119847B1 (ko) | 2005-11-08 | 2006-05-29 | 마취 각성 촉진제 |
CN200680050541.9A CN101355953B (zh) | 2005-11-08 | 2006-05-29 | 麻醉苏醒促进剂 |
EP06746949.4A EP1946763B1 (en) | 2005-11-08 | 2006-05-29 | Promoter for recovery from anesthesia |
JP2007544063A JP5246398B2 (ja) | 2005-11-08 | 2006-05-29 | 麻酔覚醒促進剤 |
US12/116,515 US20090131338A1 (en) | 2005-11-08 | 2008-05-07 | Anesthesia arousal composition |
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JP2005-323968 | 2005-11-08 | ||
JP2005323968 | 2005-11-08 |
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US12/116,515 Continuation US20090131338A1 (en) | 2005-11-08 | 2008-05-07 | Anesthesia arousal composition |
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US (1) | US20090131338A1 (ja) |
EP (1) | EP1946763B1 (ja) |
JP (1) | JP5246398B2 (ja) |
KR (1) | KR101119847B1 (ja) |
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Cited By (1)
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JP2010505826A (ja) * | 2006-10-05 | 2010-02-25 | エーザイ インコーポレイテッド | プロポフォールの水溶性プロドラッグの水ベースの薬学的製剤 |
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TWI445540B (zh) * | 2007-04-20 | 2014-07-21 | Ajinomoto Kk | 抗低體溫組成物 |
CN101721423B (zh) * | 2008-10-21 | 2012-05-23 | 曾因明 | 碳酸氢盐生理平衡液及其制备方法 |
CN101721424B (zh) * | 2008-10-21 | 2012-07-25 | 曾因明 | 碳酸氢盐生理平衡液及其制备方法 |
WO2012031125A2 (en) | 2010-09-01 | 2012-03-08 | The General Hospital Corporation | Reversal of general anesthesia by administration of methylphenidate, amphetamine, modafinil, amantadine, and/or caffeine |
RU2728778C2 (ru) | 2013-06-05 | 2020-07-31 | Трисида, Инк. | Протон-связывающие полимеры для перорального введения |
RU2713416C2 (ru) | 2014-12-10 | 2020-02-05 | Трисида, Инк. | Протон-связывающие полимеры для перорального введения |
CA3023264A1 (en) | 2016-05-06 | 2017-11-09 | Tricida, Inc. | Compositions for and method of treating acid-base disorders |
AU2018360867A1 (en) | 2017-11-03 | 2020-04-30 | Tricida, Inc. | Compositions for and method of treating acid-base disorders |
CN114984223B (zh) * | 2022-05-31 | 2023-06-20 | 中国人民解放军陆军军医大学第二附属医院 | 生长激素促分泌素受体拮抗剂在制备吸入麻醉复苏制剂中的应用 |
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WO1986000227A1 (en) * | 1984-06-22 | 1986-01-16 | Veech Richard L | Electrolyte solutions and in vivo use thereof |
JP3643879B2 (ja) * | 1993-01-11 | 2005-04-27 | 株式会社大塚製薬工場 | 電解質輸液組成物 |
KR100267604B1 (ko) * | 1993-06-04 | 2000-11-01 | 이 세갈 폴 | 혈장 유사 용액 |
US6048553A (en) * | 1997-03-17 | 2000-04-11 | Macquarie Veterinary Supplies Pty Ltd | Aqueous metal bicarbonate solution useful in treating inflammatory, degenerative and viral diseases |
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JPH10203961A (ja) * | 1997-01-21 | 1998-08-04 | Hoechst Marion Roussel Kk | 糖尿病患者用電解質輸液剤 |
JP2004149495A (ja) * | 2002-11-01 | 2004-05-27 | Shimizu Pharmaceutical Co Ltd | 電解質代謝および酸塩基平衡を管理する方法 |
Non-Patent Citations (2)
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ROTH S.H. ET AL: "Cellular mechanisms of neural excitation induced by general anesthetics", PROGRESS IN ANESTHETIC MECHANISM, vol. 6, 2000, pages 63 - 67, XP003012630 * |
See also references of EP1946763A4 * |
Cited By (1)
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JP2010505826A (ja) * | 2006-10-05 | 2010-02-25 | エーザイ インコーポレイテッド | プロポフォールの水溶性プロドラッグの水ベースの薬学的製剤 |
Also Published As
Publication number | Publication date |
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EP1946763A1 (en) | 2008-07-23 |
KR20080071173A (ko) | 2008-08-01 |
US20090131338A1 (en) | 2009-05-21 |
JPWO2007055044A1 (ja) | 2009-04-30 |
CN101355953B (zh) | 2014-07-09 |
CN101355953A (zh) | 2009-01-28 |
EP1946763B1 (en) | 2013-08-21 |
EP1946763A4 (en) | 2012-07-04 |
CN102600202A (zh) | 2012-07-25 |
JP5246398B2 (ja) | 2013-07-24 |
KR101119847B1 (ko) | 2012-03-14 |
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