WO2020262591A1 - 筋肉疲労の回復促進剤、及び、筋肉疲労の回復促進液の製造方法 - Google Patents

筋肉疲労の回復促進剤、及び、筋肉疲労の回復促進液の製造方法 Download PDF

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WO2020262591A1
WO2020262591A1 PCT/JP2020/025159 JP2020025159W WO2020262591A1 WO 2020262591 A1 WO2020262591 A1 WO 2020262591A1 JP 2020025159 W JP2020025159 W JP 2020025159W WO 2020262591 A1 WO2020262591 A1 WO 2020262591A1
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Prior art keywords
hydrate
muscle fatigue
ice
recovery
muscle
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English (en)
French (fr)
Japanese (ja)
Inventor
圭彦 杉原
裕之 村上
敬宏 江口
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Kirin Holdings Co Ltd
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Kirin Holdings Co Ltd
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Priority to US17/622,525 priority Critical patent/US20220354884A1/en
Priority to JP2021527763A priority patent/JP7212777B2/ja
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K9/10—Dispersions; Emulsions

Definitions

  • the present invention relates to a method for producing a muscle fatigue recovery promoter and a muscle fatigue recovery promoter, and more specifically, for preparing a muscle fatigue recovery promoter for application to the skin at the time of use.
  • the present invention relates to a recovery promoter, a method for producing a recovery promoter for muscle fatigue, and the like.
  • Muscle fatigue is a general term for muscle pain caused by strenuous exercise, dullness of arms and legs caused by sudden exercise, stiff shoulders caused by taking a constant posture for a long time, and low back pain. It is known that many factors are involved in muscle fatigue. Such factors include, for example, (1) accumulation of metabolic by-products (H + , inorganic phosphate, ammonia, etc.) in cells, (2) deterioration of Ca2 + release function in sarcoplasmic reticulum, and (3) necessary for muscle contraction. ATP deficiency, (4) depletion of energetic substances such as muscle glycogen and hepatic glycogen, (5) muscle damage, and the like.
  • metabolic by-products H + , inorganic phosphate, ammonia, etc.
  • ATP deficiency (4) depletion of energetic substances such as muscle glycogen and hepatic glycogen, (5) muscle damage, and the like.
  • Patent Document 1 describes a muscle fatigue improving agent containing alanyl glutamine or a salt thereof as an active ingredient
  • Patent Document 2 includes nine types such as leucine.
  • Patent Document 3 discloses a blood circulation promoting external preparation containing carbonated water, which is characterized by being applied to a target site of a living body together with ultrasonic irradiation.
  • Patent Document 3 as a method of artificially dissolving carbonic acid in water, a chemical method of putting a tablet or the like containing baking soda into water, a method of mixing carbonic acid with water and dissolving under pressure, and a method of using a static mixer , A method using a multilayer composite hollow fiber membrane, and a method of refining and dissolving air bubbles are mentioned.
  • these methods are not sufficient because they require a special device such as an ultrasonic device, which limits the environment in which the method can be performed, and may not sufficiently recover muscle fatigue. was there. Therefore, a new recovery promoter for muscle fatigue has been sought after.
  • CO 2 hydrate carbon dioxide hydrate
  • the CO 2 hydrate is a clathrate compound in which carbon dioxide molecules are trapped in the empty dimensions of water molecule crystals.
  • the water molecule that forms the crystal is called the "host molecule”
  • the guest molecule or “guest substance”.
  • CO 2 hydrate decomposes into CO 2 (carbon dioxide) and water when it melts, so it generates CO 2 when it melts.
  • CO 2 hydrate the CO 2 and water, low temperature and, can be prepared by the condition that the high pressure of CO 2 partial pressure, for example, be a certain temperature, and, CO 2 hydrate at that temperature It can be produced under conditions including a CO 2 partial pressure higher than the equilibrium pressure of the rate (hereinafter, also referred to as “CO 2 hydrate generation condition”).
  • CO 2 content of the CO 2 hydrate depending on the preparation of CO 2 hydrate, can be on the order of about 3-28 wt%, CO 2 content of the carbonated water (about 0.5 wt% ) Is significantly higher.
  • CO 2 hydrate As application of CO 2 hydrate, the addition of CO 2 hydrate beverages, it is known to mix.
  • CO 2 hydrate is mixed with a beverage to impart carbon dioxide to the beverage to produce a carbonated beverage.
  • Patent Document 5 CO 2 hydrate is covered with ice. It is disclosed that by adding the carbon dioxide supplement medium formed in the above method to the beverage, the slimy beverage is cooled and the deflated beverage is supplemented with carbon dioxide gas.
  • fresh food, dairy products, any one of the cold object of confectionery and fresh flowers a method of cold using a CO 2 hydrate, CO 2 hydrate and the cold insulating target A method of keeping an object to be kept cold by accommodating the thing in a sealable container without contact is disclosed.
  • an oxygen hydrate (O 2 hydrate) is used to cool a bather's body part, a bather's beverage, etc. to prevent spillage, and a cooling device capable of realizing a comfortable bathing environment. Is disclosed.
  • An object of the present invention is a muscle fatigue recovery accelerator that can effectively promote the recovery of muscle fatigue, and a step of bringing the muscle fatigue recovery accelerator into contact with a liquid or melting it as it is.
  • the purpose is to provide a method for producing a recovery-promoting solution.
  • the present inventors While diligently studying to solve the above problems, the present inventors applied ice (preferably CO 2 hydrate) having a CO 2 content of 3% by weight or more or its melted water to the skin of an animal body. Then, they found that the recovery of the fatigue of the muscles existing under the skin could be effectively promoted, and completed the present invention. In addition, the present inventors have so far been able to cool the body while suppressing a decrease in blood flow in the skin by cooling the body with ice having a CO 2 content of 3% by weight or more, and conventional icing. He has found that the law can be improved and has filed a patent application (Japanese Patent Application No. 2018-200952). However, such an application discloses that ice with a CO 2 content of 3% by weight or more actually promotes recovery of muscle fatigue, in particular, recovery of induced muscle strength during electrical stimulation. Not.
  • the present invention (1) An agent for promoting recovery from muscle fatigue, which is characterized by containing ice having a CO 2 content of 3% by weight or more; (2) The recovery promoter for muscle fatigue according to (1) above, wherein ice having a CO 2 content of 3% by weight or more is a CO 2 hydrate; (3) The recovery promoter for muscle fatigue according to (1) or (2) above, which is a recovery promoter for induced muscle strength during electrical stimulation after exercise; (4) Any of the above (1) to (3), wherein the ice having a CO 2 content of 3% by weight or more is an ice having a maximum length of 3 mm or more and a CO 2 content of 3% by weight or more.
  • the recovery promoter for muscle fatigue described in (5) The recovery promoter for muscle fatigue according to any one of (1) to (4) above, wherein the ice having a CO 2 content of 3% by weight or more is a consolidated CO 2 hydrate; (6)
  • the muscle fatigue recovery promoter according to any one of (1) to (5) above which is for preparing a muscle fatigue recovery promoter solution for application to the skin at the time of use. ; (7)
  • a muscle fatigue recovery-promoting solution for application to the skin which comprises a step of bringing the muscle fatigue recovery-promoting agent according to any one of (1) to (6) above into contact with the liquid or melting it as it is. Production method; Regarding.
  • a muscle fatigue recovery promoter capable of effectively promoting recovery of muscle fatigue, and a step of bringing the muscle fatigue recovery promoter into contact with a liquid or melting the muscle fatigue as it is are included. It is possible to provide a method for producing a recovery promoting liquid and the like.
  • FIG. 1 is a diagram showing the measurement results of the triceps surae muscle evoked muscle strength at the time of electrical stimulation in Test 2 of Examples described later.
  • “Before fatigue” in FIG. 1 represents the measurement result of the triceps surae muscle induced muscle strength during electrical stimulation of the subject before the fatigue task was performed, and “20 minutes after fatigue” is after the fatigue task was performed. It shows the measurement result of the triceps surae muscle evoked muscle strength at the time of electrical stimulation of the subject after the lapse of 20 minutes.
  • those measurement results are expressed as relative values (%) when the average value of the induced muscle strength of each group before fatigue is 100%.
  • FIG. 1 is a diagram showing the measurement results of the triceps surae muscle evoked muscle strength at the time of electrical stimulation in Test 2 of Examples described later.
  • “Before fatigue” in FIG. 1 represents the measurement result of the triceps surae muscle induced muscle strength during electrical stimulation of the subject before the fatigue task was performed
  • the present invention [1] An agent for promoting recovery from muscle fatigue (hereinafter, “the present invention”), which contains ice having a CO 2 content of 3% by weight or more (hereinafter, also referred to as “CO 2 high content ice”). It is also referred to as “a recovery promoter for muscle fatigue”.); [2] A method for producing a muscle fatigue recovery accelerator for application to the skin, which comprises a step of contacting the muscle fatigue recovery accelerator of the present invention with a liquid or melting it as it is (hereinafter, “the production method of the present invention”). Is also displayed.); And the like.
  • “agent” can be rephrased as “substance” or “composition”. For example, in this specification, a substance for promoting recovery of muscle fatigue and a substance for promoting recovery of muscle fatigue are used. The composition is also described.
  • the present invention also includes the following aspects.
  • a muscular fatigue recovery-promoting liquid for application to the skin which is a liquid containing 200 ppm or more of carbonic acid and contains 5 million or more ultrafine bubbles (hereinafter, “the present invention”. Also referred to as “muscle fatigue recovery promoter”);
  • An animal comprising a step of applying a CO 2 high content ice (preferably CO 2 hydrate), a muscle fatigue recovery promoter of the present invention or a muscle fatigue recovery promoter to the whole body or local skin of the animal.
  • Method for promoting recovery of muscle fatigue (hereinafter, also referred to as "method for promoting recovery of muscle fatigue of the present invention”); [5] to promote the recovery of animal muscle fatigue (preferably, to promote recovery of the induced muscle during electrical stimulation), CO 2 high content of ice (preferably CO 2 hydrate), of the present invention Use of muscle fatigue recovery promoter or muscle fatigue recovery promoter; [6] To promote recovery of muscle fatigue in animals (preferably to promote recovery of evoked muscle strength during electrical stimulation), CO 2 high content ice (preferably CO 2 hydrate), according to the present invention. A method of using the muscle fatigue recovery promoter or the muscle fatigue recovery promoter of the present invention; [7] Use of high CO 2 content ice (preferably CO 2 hydrate) in the production of the muscle fatigue recovery promoter or the muscle fatigue recovery promoter of the present invention;
  • the recovery promoter for muscle fatigue of the present invention is not particularly limited as long as it contains ice having a CO 2 content of 3% by weight or more (“CO 2 high content ice”).
  • CO 2 high content ice ice having a CO 2 content of 3% by weight or more
  • the mechanism of action of the muscle fatigue recovery-promoting agent of the present invention to exert the muscle fatigue recovery-promoting effect is not clear, since it has a muscle fatigue recovery-promoting effect higher than that of ice, ice containing high CO 2 It is considered that the physiological action due to the transdermal absorption of the high concentration of CO 2 derived from it is related.
  • the CO 2 high content ice in the present invention may be CO 2 high content ice that is not a CO 2 hydrate, but has a higher effect of promoting recovery from muscle fatigue (preferably an effect of promoting recovery of induced muscle strength during electrical stimulation). From the viewpoint of obtaining CO 2 hydrate, it is preferable to use CO 2 hydrate, and more preferably to use compacted CO 2 hydrate.
  • CO 2 high content of ice in the present invention CO 2 without using a hydrate
  • CO 2 may be used CO 2 high content of ice is not a hydrate
  • CO 2 hydrate CO 2 high content of ice the without may be used CO 2 hydrate
  • CO 2 high content of ice is not a CO 2 hydrate, it may be used in combination of CO 2 hydrate.
  • CO 2 hydrate, without the compaction CO 2 hydrate it may be used CO 2 hydrate which is not compacted, without using the CO 2 hydrate which is not consolidated, compacted CO Two hydrates may be used, or a non-compacted CO 2 hydrate and a compacted CO 2 hydrate may be used in combination.
  • CO 2 hydrate is a solid clathrate compound in which carbon dioxide molecules are trapped in the empty dimensions of water molecule crystals.
  • CO 2 hydrates are usually ice-like crystals, and when placed under standard pressure conditions and temperature conditions such that ice melts, they release CO 2 while melting.
  • the CO 2 high content ice used in the present invention preferably has a CO 2 hydrate rather than a CO 2 high content ice that is not a CO 2 hydrate, and is preferably a compacted CO 2 hydrate. More preferred. The reason is that when the recovery accelerator of the present invention is brought into contact with a liquid, CO 2 bubbles (preferably ultrafine bubbles) can be obtained at a higher concentration, and as a result, higher muscle fatigue can be obtained.
  • the "ultra fine bubble” is a fine bubble having a diameter of 1000 nm or less in a solvent such as water under normal pressure. Such ultrafine bubbles have (1) a significantly large interfacial surface area of bubbles, (2) a large pressure inside bubbles, and (3) high gas dissolution efficiency as compared with ordinary bubbles having a diameter of 1 mm or more. , (4) It has excellent characteristics such as a slow bubble rising rate.
  • An ultrafine bubble generator is usually indispensable for the generation of such ultrafine bubbles, but when CO 2 high content ice (preferably CO 2 hydrate, more preferably compacted CO 2 hydrate) is used, ultra fine bubbles are used. Fine bubbles of CO 2 (preferably ultra fine bubbles) can be easily generated without using a fine bubble generator.
  • CO 2 high content ice preferably CO 2 hydrate, more preferably compacted CO 2 hydrate
  • the CO 2 high content ice (preferably CO 2 hydrate) in the present invention has a concentration (pieces / mL) in the water of the ice water when the CO 2 high content ice is added to water. It is possible to generate ultrafine bubbles or not particularly limited, but when 300 mg of the high CO 2 content ice of the present invention is added per 1 mL of water, the ultrafine bubbles (preferably CO 2) in the water in the ice water are added.
  • Ultrafine bubble) concentration preferably 5 million pieces / mL or more, more preferably 10 million pieces / mL or more, still more preferably 20 million pieces / mL or more, more preferably 2 15 million pieces / mL or more, more preferably 30 million pieces / mL or more, more preferably 35 million pieces / mL or more, still more preferably 50 million pieces / mL or more, more preferably 75 million pieces / mL or more.
  • One million pieces / mL or more more preferably 100 million pieces / mL or more, more preferably 150 million pieces / mL or more, still more preferably 200 million pieces / mL or more, more preferably 250 million pieces / mL or more.
  • High CO 2 content ice capable of generating mL or more of ultrafine bubbles (preferably ultrafine bubbles of CO 2 ) in water can be preferably mentioned.
  • the value of the concentration of ultrafine bubbles (pieces / mL) in water may be a measured value of any measuring method capable of measuring the concentration of ultrafine bubbles, but the following measuring method may be used.
  • the measured value in R is preferable, and the measured value in the following measuring method R1 is more preferable.
  • the concentration (pieces / mL) of ultrafine bubbles in water is measured by a laser diffraction / scattering method (preferably a quantitative laser diffraction / scattering method) or a nanotracking method.
  • the concentration of ultrafine bubbles by a laser diffraction / scattering method it is preferable to measure the concentration of ultrafine bubbles with a SALD-7500 ultrafine bubble measurement system manufactured by Shimadzu Corporation.
  • the SALD-7500 Ultra Fine Bubble Measurement System is a measurement device based on the quantitative laser diffraction / scattering method.
  • the concentration of ultrafine bubbles by the nanotracking method it is preferable to measure the concentration of ultrafine bubbles with Nanosite NS300 manufactured by Malvern.
  • ultra-fine bubbles can be generated in the water (preferably, ultra-fine bubble CO 2) as the upper limit of the concentration of, but not particularly limited, the concentration of ultra-fine bubbles However, for example, it is 10 billion pieces / mL or less and 1 billion pieces / mL or less.
  • ultra-fine bubbles can be generated in the water (preferably, CO 2 Ultra fine bubble) More specific concentrations of the 5 1000000-10000000000 pieces / mL, 5 million to 1 billion pieces / mL, 10 million to 10 billion pieces / mL, 10 million to 1 billion pieces / mL, 20 million to 10 billion pieces / mL, 20 million to 1 billion pieces / mL, 25 million to 10 billion pieces / mL, 25 million to 1 billion pieces / mL, 30 million to 10 billion pieces / mL, 30 million to 1 billion pieces / mL, 350 million pieces 10 million to 10 billion pieces / mL, 35 million to 1 billion pieces / mL, 50 million to 10 billion pieces / mL, 50 million to 1 billion pieces / mL, 75 million to 10 billion pieces / mL mL, 75 million to 1 billion pieces / mL, 100 million to 10 billion pieces / mL, 100 million to 10 billion pieces / mL, 100 million to 1
  • the CO 2 content of CO 2 high content of ice in the present invention is not particularly limited as long as it is 3 wt% or more, bubbles CO 2 (preferably ultra fine bubble) higher the From the viewpoint of obtaining a higher concentration and promoting the recovery of muscular fatigue (preferably, the effect of promoting recovery of induced muscle strength at the time of electrical stimulation), it is preferably 5% by weight or more, more preferably 7% by weight or more, still more preferably. 10% by weight or more, more preferably 13% by weight or more, further preferably 16% by weight or more, more preferably 18% by weight or more.
  • the upper limit is not particularly limited, and examples thereof include 30% by weight, 28% by weight, 26% by weight, and 24% by weight.
  • More specific CO 2 content of high CO 2 content ice is 5 to 30% by weight, 7 to 30% by weight, 10 to 30% by weight, 13 to 30% by weight, 16. ⁇ 30% by weight, 18 ⁇ 30% by weight, 5 ⁇ 28% by weight, 7 ⁇ 28% by weight, 10 ⁇ 28% by weight, 13 ⁇ 28% by weight, 16 ⁇ 28% by weight, 18 ⁇ 28% by weight, 5 ⁇ 26
  • 7 to 26% by weight, 10 to 26% by weight, 13 to 26% by weight, 16 to 26% by weight, 18 to 26% by weight and the like can be mentioned.
  • CO 2 content of the CO 2 high content of ice in the present invention can be adjusted by such as "level of CO 2 partial pressure" in the production of the CO 2 high content of ice in the present invention, for example, CO 2 partial pressure
  • level of CO 2 partial pressure in the production of the CO 2 high content of ice in the present invention
  • CO 2 partial pressure When it is increased, the CO 2 content of ice having a high CO 2 content can be increased.
  • the CO 2 high content ice is CO 2 hydrate, “high and low CO 2 partial pressure”, “degree of dehydration treatment”, and “whether or not compression treatment is performed” when producing CO 2 hydrate.
  • the CO 2 content of the CO 2 hydrate can be adjusted by "high or low compression pressure in the case of compression processing" and the like.
  • all of the high CO 2 content ice (preferably CO 2 hydrate) contained in the recovery accelerator for muscle fatigue of the present invention preferably has a CO 2 content of 3% by weight or more. It also contains ice and CO 2 hydrate having a CO 2 content of less than 3% by weight within the range in which the effect of the present invention (effect of promoting recovery of muscle fatigue, preferably effect of promoting recovery of induced muscle strength at the time of electrical stimulation) can be obtained. May be.
  • the ratio (% by weight) of ice or CO 2 hydrate having a CO 2 content of less than 3% by weight to the CO 2 high content ice (preferably CO 2 hydrate) contained in the recovery accelerator for muscle fatigue of the present invention Is 10% by weight or less, preferably 5% by weight or less, more preferably 3% by weight or less, still more preferably 1% by weight or less.
  • the shape of the CO 2 high content ice (preferably CO 2 hydrate) in the present invention can be appropriately set, and for example, a substantially spherical shape; a substantially ellipsoidal shape; a substantially polyhedral shape such as a substantially rectangular parallelepiped shape; or these.
  • the shape of the above is further provided with irregularities; and the like.
  • the CO 2 high content ice (preferably CO 2 hydrate) in the present invention is a crushed piece (lump) of various shapes obtained by appropriately crushing a mass of CO 2 high content ice (preferably CO 2 hydrate). ) May be.
  • the size of the CO 2 high content ice (preferably CO 2 hydrate) in the present invention is not particularly limited and can be appropriately set.
  • the lower limit of the maximum length of the CO 2 high content ice (preferably CO 2 hydrate) in the present invention is preferably 3 mm or more, more preferably 5 mm or more, further preferably 7 mm or more, more preferably 10 mm or more, and the maximum.
  • Examples of the upper limit of the length include 150 mm or less, 100 mm or less, 80 mm or less, and 60 mm or less, and more specifically, 3 mm or more and 150 mm or less, 3 mm or more and 100 mm or less, 3 mm or more and 80 mm or less, 3 mm or more and 60 mm or less, and 5 mm or more and 150 mm or less. Examples thereof include 5 mm or more and 100 mm or less, 5 mm or more and 80 mm or less, 5 mm or more and 60 mm or less, 10 mm or more and 150 mm or less, 10 mm or more and 100 mm or less, 10 mm or more and 80 mm or less, 10 mm or more and 60 mm or less.
  • the "maximum length of CO 2- rich ice” is the longest line segment that connects two points on the surface of the block of CO 2- rich ice and passes through the center of gravity of the block. Means the length of.
  • the maximum length represents the major axis (the longest diameter)
  • the maximum length represents the diameter
  • the ice has a substantially rectangular parallelepiped shape. In some cases, it represents the length of the longest diagonal line.
  • the "minimum length of CO 2 high content ice” connects two points on the surface of the mass of CO 2 high content ice (preferably CO 2 hydrate) and defines the center of gravity of the mass. It means the length of the shortest line segment that passes through.
  • the maximum length and the minimum length can be measured by using a commercially available image analysis type particle size distribution measuring device or the like, or by applying a ruler to a mass of ice containing high CO 2 (preferably CO 2 hydrate). You can also do it.
  • the aspect ratio is preferably in the range of 1 to 5, more preferably in the range of 1 to 4.
  • CO 2 high content ice preferably CO 2 hydrate
  • the aspect ratio is preferably in the range of 1 to 3, more preferably in the range of 1 to 4.
  • CO 2 high content ice preferably CO 2 hydrate
  • the size of the CO 2 high content ice can be adjusted by the following method.
  • the maximum length of CO 2 high content ice that is not CO 2 hydrate is used when adjusting the maximum length of the mold when producing such CO 2 high content ice or when crushing the CO 2 high content ice after production. It can be adjusted by adjusting the degree of crushing of the ice cubes.
  • the maximum length of the CO 2 hydrate, adjusting the degree of crushing at the time of crushing and adjusting the maximum length of the mold to be used for compression molding of CO 2 hydrate, the CO 2 hydrate after compression molding It can be adjusted by doing so.
  • the minimum length can be adjusted by adjusting the minimum length of the mold or adjusting the degree of crushing the ice having a high CO 2 content after production.
  • the method for producing ice containing high CO 2 in the present invention is not particularly limited as long as ice containing high CO 2 can be produced.
  • a method for producing CO 2 hydrate in CO 2 high content of ice is not a method of freezing the raw water while blowing CO 2 into the raw material water under conditions that do not meet the CO 2 hydrate formation conditions and the like.
  • a method for producing a CO 2 hydrate and the gas-liquid agitation method for agitating the raw water while blowing CO 2 into the raw material water under conditions satisfying the CO 2 hydrate formation conditions satisfying the CO 2 hydrate formation conditions
  • Conventional methods such as a water spray method for spraying raw material water into CO 2 under conditions can be used.
  • the CO 2 hydrate produced by these methods is usually in the form of a slurry in which fine particles of CO 2 hydrate are mixed with unreacted water, so that the CO 2 hydrate is dehydrated in order to increase the concentration of the CO 2 hydrate. It is preferable to carry out the treatment.
  • CO 2 hydrates whose water content has become relatively low due to dehydration (that is, relatively high concentrations of CO 2 hydrates) can be compression-molded into a certain shape (for example, spherical or rectangular parallelepiped shape) with a pellet molding machine. preferable.
  • the compression-molded CO 2 hydrate can be suitably used as one of the compacted CO 2 hydrates in the present invention.
  • the compression-molded CO 2 hydrate may be used as it is in the present invention, or may be further crushed or the like if necessary.
  • a method for producing CO 2 hydrate as described above, a method using raw water is relatively widely used, but fine ice (raw ice) is used instead of water (raw water) for CO 2. And, a method of producing CO 2 hydrate by reacting under the conditions of low temperature and low pressure of CO 2 partial pressure can also be used.
  • CO 2 hydrate generation condition is a condition in which the CO 2 partial pressure (CO 2 pressure) is higher than the equilibrium pressure of the CO 2 hydrate at that temperature.
  • condition where the partial pressure of CO 2 is higher than the equilibrium pressure of CO 2 hydrate
  • Figure 2 J. Chem. Eng. Data (1991) 36, 68-71 and J. Chem. Eng. Data.
  • 53, 2182-2188 for example, the vertical axis represents CO 2 pressure and the horizontal axis represents temperature
  • CO 2 hydrate generation conditions include conditions for a combination of "within a range of -20 to 4 ° C” and "within a range of carbon dioxide pressure of 1.8 to 4 MPa" and a range of "-20 to -4 ° C”.
  • the condition of the combination of "inside” and “within the range of carbon dioxide pressure of 1.3 to 1.8 MPa” can be mentioned.
  • the content of CO 2 high content ice (preferably CO 2 hydrate) in the recovery accelerator for muscle fatigue of the present invention is not particularly limited, but is, for example, in the range of 5 to 100% by weight, preferably 30 to 100% by weight. %, More preferably 50-100% by weight, still more preferably 70-100% by weight.
  • the "consolidated CO 2 hydrate” has a CO 2 hydrate rate of 40 to 90% (preferably 50 to 90%, more preferably 60 to 90%, still more preferably 70 to 90%). It means CO 2 hydrate.
  • the CO 2 hydrate rate means the ratio of the weight of CO 2 hydrate relative to the weight of CO 2 hydrate mass (%).
  • the CO 2 hydrate rate can be calculated by the following formula (2).
  • CO 2 hydrate rate (%) ⁇ (sample weight before melting-sample weight after melting) + (sample weight before melting-sample weight after melting) ⁇ 44 x 5.75 x 18 ⁇ x 100 ⁇ melting Previous sample weight ......... Equation (2) Equation (2) will be described below.
  • sample weight before melting-Sample weight after melting is the weight of CO 2 gas contained.
  • the amount of water required to include CO 2 gas as a hydrate is calculated using the theoretical hydration number of 5.75, the molecular weight of CO 2 of 44, and the molecular weight of water of 18, and the other water constitutes the hydrate. Not considered as clathrate hydrate.
  • Examples thereof include CO 2 hydrate capable of generating ultrafine bubbles of / mL or more, more preferably 200 million cells / mL or more, more preferably 250 million cells / mL or more in water.
  • CO 2 hydrate capable of generating ultrafine bubbles of / mL or more, more preferably 200 million cells / mL or more, more preferably 250 million cells / mL or more in water.
  • a suitable compacted CO 2 hydrate in the present invention it is possible to generate ultrafine bubbles of what concentration (pieces / mL) in the molten water obtained by melting the compacted CO 2 hydrate as it is.
  • the concentration (preferably, ultrafine bubbles of CO 2 ) of ultrafine bubbles (preferably CO2 ultrafine bubbles) in the molten water is 100 million pieces / mL.
  • CO 2 hydrates capable of generating ultrafine bubbles of / mL or more in molten water include 100 to 15 billion cells / mL, 110 billion cells / mL, and 1 to 5 billion cells.
  • an ultrafine bubble can be obtained at a higher concentration, and a higher muscle fatigue recovery promoting effect (preferably, the induced muscle strength at the time of electrical stimulation) can be obtained.
  • a higher muscle fatigue recovery promoting effect preferably, the induced muscle strength at the time of electrical stimulation
  • it is preferably 7% by weight or more, more preferably 10% by weight or more, still more preferably 13% by weight or more, more preferably 16% by weight or more, still more preferably 18% by weight or more.
  • the upper limit is not particularly limited, and examples thereof include 30% by weight, 28% by weight, 26% by weight, and 24% by weight.
  • More specific CO 2 contents of the suitable compacted CO 2 hydrate in the present invention include 7 to 30% by weight, 10 to 30% by weight, 13 to 30% by weight, 16 to 30% by weight, and 18 to 30%. Weight%, 7-28% by weight, 10-28% by weight, 13-28% by weight, 16-28% by weight, 18-28% by weight, 7-26% by weight, 10-26% by weight, 13-26% by weight , 16 to 26% by weight, 18 to 26% by weight, and the like.
  • the method for producing the consolidated CO 2 hydrate in the present invention is not particularly limited, and for example, the following production method can be preferably mentioned.
  • gas-liquid agitation method for agitating the raw water while blowing CO 2 under conditions satisfying the CO 2 hydrate formation conditions feed water, spraying the raw material water in CO 2 under conditions satisfying the CO 2 hydrate formation conditions A conventional method such as a water spray method can be used.
  • the CO 2 hydrate produced by these methods is usually in the form of a slurry in which fine particles of CO 2 hydrate are mixed with unreacted water. By performing dehydration treatment and compression treatment on such a slurry, a consolidated CO 2 hydrate can be produced.
  • the dehydration treatment and the compression treatment are sequentially performed separately, for example, the dehydration treatment of the slurry is performed and then the compression treatment of the CO 2 hydrate particles is performed.
  • the dehydration treatment and the compression treatment may be performed at the same time by compressing the slurry in a situation where the water in the slurry can be discharged, but an ultrafine bubble can be obtained at a higher concentration.
  • the dehydration treatment and compression treatment at the same time, and above all, under CO 2 hydrate generation conditions. It is more preferable to perform the dehydration treatment and the compression treatment at the same time.
  • the compression treatment of the CO 2 hydrate particles and the compression treatment of the slurry can be performed using a commercially available consolidation molding machine or the like. Examples of the pressure during the compression treatment include 1 to 100 Mpa, 1 to 50 Mpa, 1 to 30 Mpa, 1 to 15 Mpa, 1 to 10 Mpa, 2.5 to 10 Mpa, and the like.
  • the CO 2 hydrate rate is usually about 40%, and when the CO 2 hydrate particles are compressed at 2.5 MPa after the sufficient dehydration treatment, the CO 2 hydrate is obtained.
  • the rate rate is usually about 60%, and when the CO 2 hydrate particles are compressed at 10 Mpa after the dehydration treatment, the CO 2 hydrate rate is usually about 70 to 90%.
  • CO 2 high content of ice in the muscle fatigue recovery promoting agent of the present invention (preferably CO 2 hydrate) consists only CO 2 and ice CO 2 high content of ice (preferably CO 2 hydrate) (hereinafter, “optionally It may also be referred to as “CO 2 high content ice containing no component (preferably CO 2 hydrate)"), but CO 2 high content further containing an arbitrary component depending on the use of the recovery promoter for muscle fatigue. It may contain ice (preferably CO 2 hydrate).
  • the recovery accelerator for muscle fatigue of the present invention is "CO 2 high content ice containing no optional component (preferably CO 2 hydrate)" or “CO 2 high content ice containing an optional component (preferably). It may be a recovery promoter for muscle fatigue consisting only of "CO 2 hydrate)", or may further contain an optional component in addition to these CO 2 high content ice (preferably CO 2 hydrate).
  • the muscle fatigue recovery accelerator of the present invention contains CO 2 high content ice other than CO 2 hydrate
  • the muscle fatigue recovery accelerator of the present invention has a temperature at which the ice does not melt during distribution and storage. And hold at pressure. Examples of such temperature and pressure include conditions of 0 ° C. or lower at normal pressure (for example, 1 atm).
  • some CO 2 hydrate production methods are excellent in storage stability and stability. Therefore, when the muscle fatigue recovery accelerator of the present invention contains CO 2 hydrate as CO 2 high content ice, the muscle fatigue recovery accelerator of the present invention is at room temperature (5 to 5 to 5) during distribution and storage.
  • the muscle fatigue recovery promoter of the present invention Is preferably held under "low temperature conditions", “high pressure conditions”, or "low temperature conditions and high pressure conditions” during distribution, storage, and the like. From the viewpoint of convenience of holding, among these, it is preferable to hold under "low temperature conditions", and it is more preferable to hold under "low temperature conditions” at normal pressure (for example, 1 atm).
  • the upper limit temperature under the above “low temperature conditions” is 10 ° C. or lower, preferably 5 ° C. or lower, more preferably 0 ° C. or lower, still more preferably -5 ° C. or lower, more preferably -10 ° C. or lower, still more preferably-. Examples include 15 ° C. or lower, more preferably ⁇ 20 ° C., and even more preferably ⁇ 25 ° C., and the lower limit temperature under the above “low temperature conditions” is -273 ° C. or higher, ⁇ 80 ° C. or higher, ⁇ 50 ° C. or higher, ⁇ 40 ° C. or higher, ⁇ 30 ° C. or higher, and the like.
  • Examples of the lower limit pressure under the above-mentioned “high pressure condition” include 1.036 atm or more, preferably 1.135 atm or more, more preferably 1.283 atm or more, and further preferably 1.480 atm or more.
  • Examples of the upper limit pressure under “high pressure conditions” include 14.80 atm or less, 11.84 atm or less, 9.869 atm or less, 7.895 atm or less, 4.935 atm or less, and the like.
  • the muscle fatigue recovery promoter of the present invention may be contained in a container.
  • the shape and material of the container are not particularly limited, and examples thereof include plastic bottle containers.
  • the concentration (pieces / mL) of ultrafine bubbles is generated in the water in the ice water. It is possible or not particularly limited, but when 300 mg of the muscle fatigue recovery promoter of the present invention is added per 1 mL of water in terms of ice having a CO 2 content of 3% by weight or more, water in the ice water.
  • the concentration (preferably ultrafine bubbles of CO 2 ) in (preferably, ultrafine bubbles of CO 2 ) is preferably 5 million cells / mL or more, more preferably 10 million cells / mL or more, still more preferably.
  • Ultrafine bubble can be generated in the water (preferably, ultra-fine bubble CO 2) as the upper limit of the concentration of, but not particularly limited, Ultrafine
  • the concentration of bubbles is 10 billion cells / mL or less and 1 billion cells / mL or less.
  • Ultrafine bubble can be generated in the water (preferably, CO 2 Ultra fine bubble) More specific concentrations of the 5 1000000-10000000000 pieces / ML, 5 million to 1 billion pieces / mL, 10 million to 10 billion pieces / mL, 10 million to 1 billion pieces / mL, 20 million to 10 billion pieces / mL, 20 million to 1 billion pieces / ML, 25 million to 10 billion pieces / mL, 25 million to 1 billion pieces / mL, 30 million to 10 billion pieces / mL, 30 million to 1 billion pieces / mL, 35 1 million to 10 billion pieces / mL, 35 million to 1 billion pieces / mL, 50 million to 10 billion pieces / mL, 50 million to 1 billion pieces / mL, 75 million to 10 billion pieces / ML, 75 million to 1 billion pieces / mL, 100 million to 10 billion pieces / mL, 100 million to 1 billion pieces / mL, 150 million to 10
  • the measured value of the ultrafine bubble concentration in water in ice water is preferably the measured value by the above-mentioned measuring method R. It is more preferable that the values are measured by the following measurement method R2. (Measurement method R2) To 25 ° C. water, a -80 ⁇ 0 ° C.
  • CO 2 content in terms of 3% or more by weight of ice was added 300 mg / mL, CO 2 content of 3 wt% or more
  • concentration (pieces / mL) of ultrafine bubbles in the water in the ice water is determined by laser diffraction / scattering method (preferably quantitative laser diffraction / scattering method) or. Measure by nanotracking method.
  • the muscle fatigue recovery promoter of the present invention contains ice containing high CO 2 as an essential component, but the effect of the present invention (muscle fatigue recovery promoting effect, preferably, recovery promotion of induced muscle strength at the time of electrical stimulation) Any component may be further contained as long as it does not interfere with the effect).
  • optional components include components having medicinal properties, additives and the like.
  • the component having such a medicinal effect include other muscle fatigue recovery promoters, analgesics, anti-inflammatory agents and the like, and examples of the above-mentioned additives include fragrances, colorants, thickeners, pH adjusters and the like. ..
  • the type of animal to which the muscle fatigue recovery promoter or the muscle fatigue recovery promoter of the present invention is applied is not particularly limited, but is selected from a group consisting of mammals, birds, reptiles, amphibians, and fish.
  • Animals belonging to the class of mammals are preferably mentioned, among which animals belonging to mammals or birds are more preferably mentioned, among which animals belonging to mammals are more preferably mentioned, among which humans, dogs, cats, horses, ponies, donkeys, etc.
  • Cows, pigs, sheep, goats, rabbits, monkeys, mice, rats, hamsters, guinea pigs, ferrets and the like are more preferably mentioned, and humans and horses are more preferably mentioned, and humans are particularly preferred.
  • a thoroughbred which is a racehorse
  • the racehorse runs at full power in the race, and the muscle fatigue of the racehorse after the race is extremely severe.
  • Examples of animals to which the muscle fatigue recovery promoter and the muscle fatigue recovery promoter of the present invention are applied include animals in which part or all of the muscles are fatigued. More specific uses of the muscle fatigue recovery-promoting agent and the muscle fatigue recovery-promoting solution of the present invention include, for example, an agent for promoting recovery of muscle fatigue of the body before, during, and after exercise; Agents for promoting recovery from chronic muscle fatigue; etc.
  • Examples of the application site of the muscle fatigue recovery promoter and the muscle fatigue recovery promoter of the present invention include the whole body or local skin of an animal.
  • the term "whole body” means the whole body within the range in which the animal can secure breathing when the muscle fatigue recovery promoter or the muscle fatigue recovery promoter of the present invention is applied to an animal, for example, a mammal. If so, it usually means that the skin other than the head, that is, the neck and below is immersed in the muscle fatigue recovery promoter or the muscle fatigue recovery promoter of the present invention.
  • the local part is not particularly limited as long as it is a body part, and examples thereof include a head, a face, a neck, a shoulder, an arm, a hand, a chest, an abdomen, a buttocks, a leg, and a foot.
  • the muscle fatigue recovery promoter or the muscle fatigue recovery promoter of the present invention may be applied to a plurality of parts of the body at the same time.
  • the "skin" in the present specification is not particularly limited as long as it is animal skin, and also includes animal mucous membranes for convenience. Examples of such mucous membranes include lips and oral mucosa.
  • a method of applying the muscle fatigue recovery promoter of the present invention to the skin (that is, contacting the skin) or contacting the muscle fatigue recovery promoter with a liquid As a method of using the muscle fatigue recovery promoter of the present invention, a method of applying the muscle fatigue recovery promoter of the present invention to the skin (that is, contacting the skin) or contacting the muscle fatigue recovery promoter with a liquid.
  • a method of applying (that is, contacting with the skin) the muscle fatigue recovery-promoting solution of the present invention produced by allowing or melting the muscle fatigue as it is is preferably mentioned, and more specifically, the recovery of muscle fatigue of the present invention.
  • a method in which the accelerator is applied directly to the skin (that is, in direct contact with the skin) hereinafter, also referred to as “method 1”) or the recovery accelerator for muscle fatigue of the present invention is applied to the skin via a fiber material.
  • a method of application that is, the recovery promoter of the muscle fatigue of the present invention is brought into contact with the fiber material and the fiber material is brought into contact with the skin
  • method 2 A method of applying the recovery-promoting solution to the skin (that is, bringing it into contact with the skin) (hereinafter, also referred to as “method 3”) is preferably used.
  • the muscle fatigue recovery-promoting agent of the present invention is preferably for preparing a muscle fatigue recovery-promoting solution for application to the skin at the time of use.
  • the method 1 is not particularly limited as long as it is a method in which the muscle fatigue recovery promoter of the present invention is directly applied to the skin (that is, in direct contact with the skin), and the muscle fatigue recovery promoter of the present invention is put into a container.
  • the muscle fatigue recovery promoter of the present invention When the muscle fatigue recovery promoter of the present invention is brought into contact with the skin, a part of the CO 2 high-containing ice is melted to generate the muscle fatigue recovery promoter of the present invention, which causes the muscle fatigue of the present invention. Not only the recovery-promoting agent but also the recovery-promoting solution for muscle fatigue of the present invention comes into direct contact with the skin.
  • the muscle fatigue recovery promoter of the present invention is applied to the skin via the fiber material (that is, the muscle fatigue recovery promoter of the present invention is brought into contact with the fiber material, and the fiber material is applied to the skin.
  • the fiber material is applied to the skin.
  • the molten water of high CO 2 content ice (preferably CO 2 hydrate) is brought into contact with one surface of the fiber material, the molten water is the opposite surface of the fiber material.
  • the material shape; whether it is a woven fabric, a non-woven fabric, a sponge, etc.; is not particularly limited.
  • Examples of the material of the above fiber material include natural fibers such as cotton, wool, cupra, silk, capoc, flax, cannabis, yellow hemp, linseed, kenaf, bashofu, and coconut, nylon, polypropylene, polyethylene, polyamide, polyester, Synthetic fibers such as polyacrylic and polyurethane and blended fibers thereof can be mentioned, and among these, cotton is preferable.
  • the recovery accelerator muscle fatigue of the invention the through fiber material is contacted with the skin, CO 2 part of the high content of ice is melted, promoting the recovery liquid muscle fatigue of the invention occurs, the The recovery-promoting liquid permeates the fiber material and comes into direct contact with the skin.
  • the shape of the fiber material examples include a sheet shape and a bag shape, and a bag shape is preferable from the viewpoint of ease of use.
  • a bag shape is preferable from the viewpoint of ease of use.
  • the muscle fatigue recovery promoter of the present invention is put in a long bag-shaped fiber material and the long bag-shaped fiber material is wrapped around a body part such as a leg, "the muscle fatigue recovery promoter of the present invention” is obtained.
  • melted water of high CO 2 content ice (preferably CO 2 hydrate) contained in the agent” can be stably brought into contact with the skin of the body part.
  • the above method 3 is not particularly limited as long as it is a method of applying the muscle fatigue recovery promoting solution of the present invention to the skin (that is, bringing it into contact with the skin), and the muscle fatigue recovery promoting solution of the present invention is placed in a container such as a bucket.
  • the amount of the muscle fatigue recovery promoter of the present invention to be used includes the area of the skin to which the muscle fatigue recovery promoter and the muscle fatigue recovery promoter of the present invention are applied, the degree of muscle fatigue, and the muscle fatigue recovery promoter. It can be set as appropriate according to the usage method of.
  • the recovery accelerator for muscle fatigue of the present invention is added in an amount of 0.3 to 30 g, preferably 1 to 25 g, in terms of CO 2 high content ice (preferably CO 2 hydrate) per 25 cm 2 of the skin.
  • the fiber material 25 cm 2 per a recovery accelerator muscle fatigue of the present invention CO 2 high content of ice (preferably CO 2 hydrate) converted at 0.3 ⁇ 30 g , Preferably 1 to 25 g, more preferably 2 to 10 g, and in the above method 3, the amount of CO 2 high-containing ice used (preferably the amount added) used when preparing the recovery-promoting solution for muscle fatigue of the present invention. ) (Mg / mL) includes the amount described in the item of the production method of the present invention described later.
  • the temperature of the muscle fatigue recovery promoting solution can be appropriately set, for example, 0 to 20 ° C, 0 to 15 ° C, 0 to 10. ° C, 0-8 ° C, 0-6 ° C, 0-4 ° C, 0-3 ° C, 0-2 ° C, 2-20 ° C, 2-15 ° C, 2-10 ° C, 2-8 ° C, 2-6 ° C., 2 to 4 ° C., 4 to 20 ° C., 4 to 15 ° C., 4 to 10 ° C., 4 to 8 ° C., 4 to 6 ° C. and the like.
  • the method for adjusting the temperature of the muscle fatigue recovery accelerator of the present invention is not particularly limited, and for example, a method for adjusting the temperature of the liquid in contact with the muscle fatigue recovery accelerator or the temperature of the muscle fatigue recovery accelerator is used.
  • a method of adjusting the temperature with a cooling device or a heating device is used.
  • a cooling device and a heating device commercially available ones can be used.
  • the CO 2- rich ice (preferably CO 2 hydrate) in the muscle fatigue recovery-promoting agent of the present invention is usually a solid, and the CO 2- rich ice is brought into contact with the liquid to prepare a muscle fatigue recovery-promoting solution.
  • the temperature of the liquid usually drops relatively significantly because it draws a lot of heat from the liquid as it melts or part of the high CO 2 content ice. Therefore, when the muscle fatigue recovery promoter of the present invention is brought into contact with the liquid to prepare the muscle fatigue recovery promoter, it is preferable to use a liquid having a temperature higher than the desired temperature of the muscle fatigue recovery promoter. For example, it is preferable to use a liquid having a temperature 2 ° C. or higher, 4 ° C. or higher, or 6 ° C.
  • the muscle fatigue recovery promoting solution of the present invention is prepared before use when applied to the skin from the viewpoint of obtaining a higher muscle fatigue recovery promoting effect (preferably, a recovery promoting effect of induced muscle strength at the time of electrical stimulation). Is preferable.
  • "preparing at the time of use” is calculated from the time when the application of the muscle fatigue recovery promoting solution to the skin is started (the time when the contact of the muscle fatigue recovery promoting solution to the skin is started). For example, within 1 hour, preferably within 40 minutes, more preferably within 30 minutes, further preferably within 20 minutes, more preferably within 10 minutes, still more preferably within 5 minutes. Includes preparing a recovery-promoting solution for muscle fatigue.
  • the surface temperature of the muscle fatigue recovery accelerator can be appropriately set, even if it is less than ⁇ 20 to 0 ° C. It is good, but 0 to 3 ° C. and the like can be mentioned.
  • the effect of the present invention (effect of promoting recovery of muscle fatigue, preferably effect of promoting recovery of induced muscle strength at the time of electrical stimulation) is obtained as the application time of the recovery promoter for muscle fatigue and the recovery promoter for muscle fatigue of the present invention.
  • the muscle fatigue recovery promoter or muscle fatigue recovery promoter of the present invention is applied to the skin at the application site, for example, for 3 to 30 minutes, 5 to 25 minutes, 5 to Contacting may be performed for 20 minutes, 5 to 15 minutes, 10 to 20 minutes, and 10 to 15 minutes.
  • the frequency of application of the muscle fatigue recovery promoter and the muscle fatigue recovery promoter of the present invention is not particularly limited and may be appropriately determined based on the improvement of symptoms, for example, once every 1 to 3 days. About 3 times can be mentioned.
  • CO 2 high content ice the CO 2 high content ice, the muscle fatigue recovery accelerator of the present invention, or the muscle fatigue recovery promotion solution of the present invention (hereinafter, collectively referred to as "CO 2 high content ice, etc.”).
  • “Has a muscle fatigue recovery promoting effect” means that the tired muscles are compared with the case where no treatment is applied to the tired muscles or when normal ice is applied to the tired muscles. This means that when ice containing high CO 2 content is applied to the skin of the site, recovery from muscle fatigue is promoted.
  • the index for recovery from fatigue of such muscles is not particularly limited, but recovery of induced muscle strength at the time of electrical stimulation in such muscles is preferably mentioned.
  • ice containing high CO 2 "has the effect of promoting recovery from muscle fatigue” means that the tired muscle is not treated (for example, when it is left for 15 to 25 minutes or 20 minutes) or the tired muscle.
  • CO 2 high content ice or the like when CO 2 high content ice or the like is applied to tired muscles (for example, when applied for 15 to 25 minutes or 20 minutes). When applied), it includes the suppression of the decrease in induced muscle strength due to fatigue.
  • the fact that the decrease in induced muscle strength due to fatigue is suppressed means that when the degree of decrease in induced muscle strength due to fatigue is 10 (reference value) when no treatment is applied to the tired muscle, after fatigue the application of such CO 2 high content of ice, the degree of reduction in the induced muscle fatigue (relative value when the reference value of the above was 10) is 8 or less, preferably 5 or less, more preferably 3 or less, more preferably It is included that the muscle strength is suppressed to 2 or less, and most preferably, the induced muscle strength is restored to the induced muscle strength before fatigue by applying CO 2 high content ice or the like after fatigue.
  • the CO 2 high content ice (preferably CO 2 hydrate) is CO 2 .
  • the CO 2 high content ice (preferably CO 2 hydrate) is CO 2 .
  • hydrophilic solvent (ii) ". Examples thereof include “hydrophobic solvent”, (iii) “mixed solvent of hydrophilic solvent and hydrophobic solvent”, “liquid containing any solute in any of the solvents (i) to (iii)” and the like.
  • the temperature and pressure conditions under which the "liquid” in the present invention is in a liquid state cannot be unequivocally specified because they depend on the type of solvent, the use of the liquid, the conditions of use of the liquid, and the like.
  • a liquid that is liquid under atmospheric pressure conditions is preferred.
  • solubility parameter (SP value) 20 or more is preferable, and 29.9 or more is more preferable.
  • SP value solubility parameter
  • Divalent alcohols such as ethylene glycol (29.9), diethylene glycol (24.8), triethylene glycol (21.9), tetraethylene glycol (20.3), and propylene glycol (25.8) as polyhydric alcohols.
  • the preferred hydrophilic solvent in the present invention preferably contains at least water, and more preferably water.
  • the "hydrophobic solvent” used in the present invention is preferably an organic solvent having a solubility parameter (SP value) of less than 20.0, and specifically, preferably a hydrocarbon solvent, a silicone solvent, or a solvent thereof. Is a mixture of.
  • hydrocarbon solvents for example, hexane (14.9), heptane (14.3), dodecane (16.2), cyclohexane (16.8), methylcyclohexane (16.1), octane (16.0).
  • Aliphatic hydrocarbons such as hydrogenated triisobutylene, aromatic hydrocarbons such as benzene (18.8), toluene (18.2), ethylbenzene (18.0), xylene (18.0), chloroform (19. Halogen-based hydrocarbons such as 3), 1,2, dichloroethane (19.9), and trichloroethylene (19.1) can be exemplified, and examples of the silicone-based solvent include octamethylcyclotetrasiloxane and decamethylcyclopenta. Examples thereof include siloxane, hexamethyldisiloxane, and octamethyltrisiloxane. Of these, hexane (14.9) and cyclohexane (16.8) are particularly preferable. Two or more of these hydrophobic solvents may be used in combination.
  • the "solute” in the above "liquid containing any solute in any of the solvents (i) to (iii)” includes ice containing high CO 2 (preferably CO 2 hydrate) in the liquid.
  • the ice is not particularly limited as long as the CO 2 high content ice (preferably CO 2 hydrate) can generate CO 2 bubbles (preferably ultrafine bubbles), and examples thereof include carbon dioxide and salt.
  • Specific examples of the "liquid containing any solute in any of the solvents (i) to (iii)” include melted water of ice having a high CO 2 content and physiological saline, and ice having a high CO 2 content.
  • the melted water of CO 2 hydrate is preferably mentioned, and the melted water of CO 2 hydrate is more preferably mentioned. Melted water of ice containing high CO 2 such as CO 2 hydrate contains carbon dioxide as a solute.
  • the "muscle fatigue recovery-promoting solution” in the present specification is not necessarily limited to the case where all are liquid, and may be a mixture of solid CO 2 high-containing ice (preferably CO 2 hydrate) and liquid. included.
  • ice having a high CO 2 content (preferably CO 2 hydrate) and a liquid are used.
  • the method is not particularly limited as long as it is brought into contact with the liquid, and a method of containing CO 2 high content ice (preferably CO 2 hydrate) in the liquid is preferable.
  • CO 2 high content ice preferably CO 2 hydrate
  • the method of adding or adding the liquid to the liquid and the method of adding or adding the liquid to the CO 2 high content ice (preferably CO 2 hydrate) are more preferable, and among them, the CO 2 high content ice (preferably CO 2 hydrate) is added or added.
  • a method of adding or adding rate) to the liquid is more preferable.
  • the amount of CO 2 high content of ice in the case of contacting the CO 2 high content of ice in the liquid is, CO 2 high content ice CO 2 hydrate Whether or not it is a compacted CO 2 hydrate, the CO 2 content of ice with a high CO 2 content, or what concentration of CO 2 bubbles (preferably ultrafine bubbles) are required.
  • a person skilled in the art can appropriately set it depending on whether or not to do so.
  • the amount (preferably added amount) (mg / mL) of ice containing high CO 2 content for example, 10 mg / mL or more can be mentioned, and CO 2 bubbles (preferably ultrafine bubbles) can be obtained at a higher concentration.
  • CO 2 bubbles preferably ultrafine bubbles
  • 20 mg / mL or more more preferably 50 mg / mL or more, still more preferably 100 mg / mL or more, more preferably 150 mg / mL or more, still more preferably 200 mg / mL or more.
  • the upper limit of the amount (preferably added amount) (mg / mL) of ice containing high CO 2 is not particularly limited, but for example, 5000 mg / mL or less, 3000 mg / mL or less, 2000 mg / mL or less, 1000 mg / mL.
  • 500 mg / mL or less can be mentioned.
  • the amount of CO 2 high-containing ice used (preferably added amount) (mg / mL), 20 to 5000 mg / mL, 20 to 3000 mg / mL, 20 to 2000 mg / mL, 50 to Examples thereof include 2000 mg / mL, 50 to 1000 mg / mL, 100 to 500 mg / mL, and 150 to 500 mg / mL.
  • the amount of CO 2 high content ice used (mg / mL) means the weight (mg) of CO 2 high content ice used per 1 mL of the liquid (preferably added).
  • the temperature of the liquid when the ice containing high CO 2 is brought into contact with the liquid is not particularly limited as long as CO 2 bubbles (preferably ultrafine bubbles) are generated, and is, for example, 0 to 50 ° C, 0 to 35 ° C, 0.
  • the CO 2- rich ice (preferably CO 2 hydrate) in the muscle fatigue recovery-promoting agent of the present invention is usually a solid, and when the CO 2- rich ice is brought into contact with a liquid to prepare a muscle fatigue recovery-promoting liquid.
  • the temperature of a liquid usually drops relatively significantly because it draws a lot of heat from the liquid as it melts or part of the high CO 2 content ice. Therefore, when the muscle fatigue recovery promoter of the present invention is brought into contact with the liquid to prepare the muscle fatigue recovery promoter, it is preferable to use a liquid having a temperature higher than the desired temperature of the muscle fatigue recovery promoter.
  • a liquid having a temperature higher than the desired temperature of the prepared muscle fatigue recovery promoting liquid by 2 ° C. or higher, 4 ° C. or higher, or 6 ° C. or higher, preferably 2 to 10 ° C., 4 to 10 ° C., 6 to 10 ° C. It is preferable to use a liquid of temperature.
  • the temperature at which ice with a high CO 2 content (preferably CO 2 hydrate) melts is not particularly limited as long as it is a method of exposing CO 2 high content ice (preferably CO 2 hydrate) under the conditions.
  • CO 2 high content ice preferably CO 2 hydrate
  • Examples include a method of placing the product under the condition of °C.
  • CO 2 The amount of CO 2 high content of ice case of high content of ice as it melted, mention may be made of the same weight and promoting the recovery liquid muscle fatigue needed.
  • the muscle fatigue recovery promoting solution of the present invention is a muscle fatigue recovery promoting solution for application to the skin.
  • the muscular fatigue recovery promoting solution of the present invention is not particularly limited as long as it is a liquid containing 200 ppm or more of carbonic acid and contains 5 million or more ultrafine bubbles, but is not particularly limited. It is preferably a recovery-promoting solution for muscle fatigue produced by the production method.
  • the “muscle fatigue recovery-promoting solution” in the present specification is not necessarily limited to the case where all are liquid, and the solid CO 2 high-containing ice (preferably CO 2 hydrate) and the liquid. It is also included when it is a mixture.
  • the muscle fatigue recovery promoting solution of the present invention is not particularly limited as long as it contains 200 ppm or more of carbonic acid, but is preferably 500 ppm (0.05% by weight) or more, more preferably 750 ppm (0.075% by weight) or more, and further. It preferably contains 900 ppm (0.09% by weight) or more, more preferably 1000 ppm (0.1% by weight) of carbonic acid.
  • the upper limit of carbonic acid is not particularly limited, but for example, 5000 ppm (0.5% by weight) or less, 4000 ppm (0.4% by weight) or less, 3000 ppm (0.3% by weight) or less, 2000 ppm (0.2% by weight) or less, 1500 ppm (0.15% by weight) or less can be mentioned.
  • the carbonic acid concentration in the muscle fatigue recovery promoting solution of the present invention is 500 to 5000 ppm, 750 to 5000 ppm, 900 to 5000 ppm, 1000 to 5000 ppm, 500 to 4000 ppm, 750 to 4000 ppm, 900 to 4000 ppm, 1000 to 4000 ppm. , 500-3000ppm, 750-3000ppm, 900-3000ppm, 1000-3000ppm, 500-2000ppm, 750-2000ppm, 900-2000ppm, 1000-2000ppm, 500-1500ppm, 750-1500ppm, 900-1500ppm, 1000-1500ppm, etc. Can be mentioned.
  • the carbonic acid concentration in the muscle fatigue recovery promoting solution of the present invention means the concentration measured at a liquid temperature of 0 to 2 ° C. and under normal pressure.
  • the value of the concentration of ultrafine bubbles (preferably ultrafine bubbles of CO 2 ) in the muscle fatigue recovery promoting solution of the present invention is not particularly limited as long as it is 5 million pieces / mL or more, but is preferably 1,000. 10,000 pieces / mL or more, more preferably 20 million pieces / mL or more, further preferably 25 million pieces / mL or more, more preferably 30 million pieces / mL or more, still more preferably 35 million pieces. / ML or more, more preferably 50 million pieces / mL or more, further preferably 75 million pieces / mL or more, more preferably 100 million pieces / mL or more, still more preferably 150 million pieces / mL or more.
  • ultra-fine bubbles in the recovery accelerating liquid muscle fatigue of the invention the upper limit of the concentration of, but not particularly limited, for example, 10 billion cells / mL or less, 1 billion / It may be less than mL.
  • Ultrafine bubble in the recovery accelerating liquid muscle fatigue of the invention as a more specific concentrations of 5 1000000-10000000000 cells / mL, 5 1000000-1000000000 pieces / ML, 10 million to 10 billion pieces / mL, 10 million to 1 billion pieces / mL, 20 million to 10 billion pieces / mL, 20 million to 1 billion pieces / mL, 25 million to 100 100 million pieces / mL, 25 million to 1 billion pieces / mL, 30 million to 10 billion pieces / mL, 30 million to 1 billion pieces / mL, 35 million to 10 billion pieces / mL, 3 15 million to 1 billion pieces / mL, 50 million to 10 billion pieces / mL, 50 million to 1 billion pieces / mL, 75 million to 10 billion pieces / mL, 75 million to 10 100 million pieces / mL, 100 million to 10 billion pieces / mL, 100 million to 10 billion pieces / mL, 100 million to 1 billion pieces / mL
  • Ultra-fine bubbles in the recovery accelerating liquid muscle fatigue of the invention (preferably, ultra-fine bubble CO 2)
  • the value of the concentration it is possible to measure the concentration of ultra-fine bubbles, a measure of any assay although it may be present, it is preferably the measured value by the above-mentioned measuring method R, and more preferably the measured value by the above-mentioned measuring method R1 or R2.
  • the temperature of the muscle fatigue recovery promoting solution of the present invention can be appropriately set according to the state of the muscle at the application site, for example, 0 to 20 ° C, 0 to 15 ° C, 0 to 10 ° C, 0 to 8. ° C, 0-6 ° C, 0-4 ° C, 0-3 ° C, 0-2 ° C, 2-20 ° C, 2-15 ° C, 2-10 ° C, 2-8 ° C, 2-6 ° C, 2-4 ° C., 4 to 20 ° C., 4 to 15 ° C., 4 to 10 ° C., 4 to 8 ° C., 4 to 6 ° C. and the like.
  • the method for producing the muscle fatigue recovery promoting solution of the present invention is as described in "2.” above.
  • the muscle fatigue recovery promoting solution of the present invention may be contained in a container.
  • the shape and material of the container are not particularly limited, and examples thereof include plastic bottle containers.
  • the method for promoting recovery from muscle fatigue of the present invention is a method for promoting recovery from muscle fatigue in animals.
  • a CO 2 high-containing ice preferably CO 2 hydrate
  • a muscle fatigue recovery promoter of the present invention or a muscle fatigue recovery promoter solution is used in an animal (for example, non-human). It is not particularly limited as long as it includes a step of applying to the whole body or local skin of (animal).
  • a method of applying for example, contacting) a high CO 2 content ice (preferably CO 2 hydrate), a muscle fatigue recovery promoter or a muscle fatigue recovery promoter of the present invention to the whole body or local skin of an animal.
  • a high CO 2 content ice preferably CO 2 hydrate
  • a muscle fatigue recovery promoter or a muscle fatigue recovery promoter of the present invention to the whole body or local skin of an animal.
  • methods 1 to 3 that is, a method of directly applying (that is, directly contacting) the skin with the recovery promoter of the muscle fatigue of the present invention (“method 1”), or the muscle fatigue of the present invention.
  • Method 2 the method of applying the recovery promoter of the present invention to the skin via the fiber material (that is, contacting the recovery promoter of the muscle fatigue of the present invention with the fiber material and bringing the fiber material into contact with the skin)
  • Method 3 the method of applying the recovery-promoting solution for muscle fatigue of the present invention to the skin (that is, bringing it into contact with the skin) is preferably mentioned.
  • Test 1 [Preparation of CO 2 hydrate] Blowing 4L of water to CO 2 gas such that the 3 MPa, stirring the while allowed to proceed CO 2 hydrate formation reaction at 1 ° C., CO 2 hydrate particles are suspended in water "CO 2 hydrate slurry I got. The slurry was poured into a cylinder-type consolidation molding machine and compressed at a maximum pressure of 1 MPa for 3 minutes to remove water from the CO 2 hydrate slurry. Next, the CO 2 hydrate particles are squeezed at a pressure of 10 MPa, cooled to ⁇ 20 ° C., and after recovering the consolidated cylindrical mass of the consolidated CO 2 hydrate from the consolidation molding machine, the cylindrical mass Was crushed.
  • a compacted CO 2 hydrate having a maximum length of 3 mm or more and 60 mm or less (hereinafter, simply referred to as “CO 2 hydrate” in this example) was selected and recovered, and used in the subsequent experiments.
  • the CO 2 content of this CO 2 hydrate was 20 to 25%, and the CO 2 hydrate rate was about 72 to 89%.
  • the concentration (pieces / mL) of ultrafine bubbles in the molten water of this CO 2 hydrate was measured using "Nanosite NS300" manufactured by Malvern, and found to be about 1.3 billion pieces / mL. Further, the carbonic acid concentration of the molten water of this CO 2 hydrate contains carbonic acid of 2000 ppm or more.
  • Three groups (36 subjects in total) were prepared with 12 subjects as one group.
  • the three groups were a CO 2 hydrate group, an ice group, and a non-contact group, respectively.
  • "exercise of ankle plantar flexion muscle strength for 3 seconds-3 seconds rest” was performed 40 times x 2 sets (rest between sets: 1 minute). Then, moisten the skin of each of the three muscles (medial gastrocnemius, lateral gastrocnemius, soleus) of the triceps surae muscle of the subject in the CO 2 hydrate group with CO 2 hydrate melted water.
  • the muscle strength before fatigue that is, immediately before performing the fatigue task
  • the muscle strength after contacting the CO 2 hydrate or ice for 20 minutes, and for the non-contact group Measured the muscle strength before fatigue and the muscle strength after fatigue (after leaving for 20 minutes after performing the fatigue task).
  • the induced muscle strength induced torque
  • Induced muscle strength is obtained by applying electrical stimulation to the triceps surae muscle using a constant current electrical stimulator (DS7A and DS7AH, manufactured by Digitimer) to induce muscle contraction, and the muscle strength at that time is measured by a muscle strength meter (CON-TREX MJ). (Registered trademark), manufactured by PHYSIOMED) was used for measurement.
  • the method of applying the electrical stimulation is as described below, and the intensity of the electrical stimulation to be applied was determined as follows.
  • a negative electrode (disposable ground electrode, manufactured by Gadelius Medical Co., Ltd.) was attached proximal to the patella, and an alligator clip was attached.
  • a positive electrode (Red Dot (registered trademark), manufactured by 3M Japan Ltd.) was attached to the back of the knee, and an alligator clip was attached in the same manner as the negative electrode.
  • the subject In order to determine the position of the positive electrode, the subject was in a standing position, and a weak current was applied to the back of the knee with wet cotton wool sandwiched between alligator clips. When the electric current flows through the nerves, the muscles contract and the legs move in the plantar flexion direction. Taking advantage of this, the part where the leg part bends most was searched for, and that part was determined as the position where the positive electrode was attached. After attaching both electrodes, the intensity of electrical stimulation was determined. The subject lay in a prone position on a muscle strength meter (CON-TREX MJ (registered trademark), manufactured by PHYSIOMED), and was fixed so that the ankle joint and the center of rotation of the muscle strength meter were aligned.
  • CON-TREX MJ registered trademark
  • the angle of the ankle joint was set to 0 °.
  • the voltage was increased by 10 mV from 30 mV to increase the strength of the current, and the torque (muscle strength) at each voltage was confirmed.
  • An electric current was passed through the muscles while gradually increasing the voltage until the torque value became constant.
  • the increase in torque value is 0.2 Nm or less when the voltage is increased by 10 mV, it is evaluated that the torque value is constant, and the voltage value before the final voltage increase by 10 mV is 1.2 times.
  • the value obtained was taken as the voltage of the electrical stimulation used in the experiment (that is, the strength of the electrical stimulation).
  • the increase in torque value was 0.2 Nm or less even when 60 mv was increased to 70 mv, 72 mv, which was obtained by multiplying 60 by 1.2, was determined as the voltage of the electrical stimulation used in the experiment.
  • the induced torque due to electrical stimulation at rest was confirmed at the determined voltage.
  • the subject was instructed to rest, and electrical stimulation (twitch torque) with simple contraction was performed twice by pre-measurement, and electrical stimulation (triplet torque) with strong contraction was performed twice at 10-second intervals. It was.
  • the output torque signal was recorded on a personal computer using an A / D converter (PowerLab 16/35, manufactured by AD Instruments) and dedicated software (LabChARt8, manufactured by AD Instruments). It should be noted that such a method for measuring the induced torque is a non-invasive method and does not harm the research subject.
  • the muscle strength before fatigue ie, just before performing the fatigue task
  • the muscle strength after contact with CO 2 hydrate or ice for 20 minutes are measured.
  • the muscle strength before fatigue and the muscle strength after fatigue were measured.
  • the average value of the induced muscle before fatigue as 100%, after contacting the CO 2 hydrate 20 minutes at fatigue after the 20 min (CO 2 hydrate group of each group, the ice in the ice group 20
  • the average value of the induced muscular strength after contacting for 1 minute and leaving for 20 minutes in the non-contact group is shown in FIG.
  • a muscle fatigue recovery promoter capable of effectively promoting recovery of muscle fatigue
  • a muscle fatigue recovery promoter solution comprising a step of bringing the muscle fatigue recovery promoter into contact with a liquid.

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PCT/JP2020/025159 2019-06-28 2020-06-26 筋肉疲労の回復促進剤、及び、筋肉疲労の回復促進液の製造方法 Ceased WO2020262591A1 (ja)

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JP2009120606A (ja) * 2007-10-25 2009-06-04 Neochemir Inc 筋力増強のための二酸化炭素供給手段の使用
WO2019035405A1 (ja) * 2017-08-17 2019-02-21 雅也 田中 二酸化炭素外用剤
US20190083298A1 (en) * 2017-09-21 2019-03-21 Michael W. Starkweather Whole body cryotherapy system
JP2020070295A (ja) * 2018-10-25 2020-05-07 キリンホールディングス株式会社 血流促進剤、及び、血流促進用液の製造方法

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CN100469425C (zh) * 2001-08-28 2009-03-18 三菱丽阳株式会社 碳酸泉和碳酸水的制造装置及制造方法、及其应用的气体浓度控制方法和膜组件
TW201503893A (zh) * 2013-06-27 2015-02-01 三菱麗陽股份有限公司 含有碳酸水的血液循環促進外用劑、爲了該劑的血液循環促進用裝置，使用該劑的血液循環促進方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009120606A (ja) * 2007-10-25 2009-06-04 Neochemir Inc 筋力増強のための二酸化炭素供給手段の使用
WO2019035405A1 (ja) * 2017-08-17 2019-02-21 雅也 田中 二酸化炭素外用剤
US20190083298A1 (en) * 2017-09-21 2019-03-21 Michael W. Starkweather Whole body cryotherapy system
JP2020070295A (ja) * 2018-10-25 2020-05-07 キリンホールディングス株式会社 血流促進剤、及び、血流促進用液の製造方法

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