WO2006073162A1 - Methode d'amelioration de la stabilite au stockage du nadh ou du nadph ou d'un sel de ces composes - Google Patents

Methode d'amelioration de la stabilite au stockage du nadh ou du nadph ou d'un sel de ces composes Download PDF

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Publication number
WO2006073162A1
WO2006073162A1 PCT/JP2006/300049 JP2006300049W WO2006073162A1 WO 2006073162 A1 WO2006073162 A1 WO 2006073162A1 JP 2006300049 W JP2006300049 W JP 2006300049W WO 2006073162 A1 WO2006073162 A1 WO 2006073162A1
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Prior art keywords
cyclodextrin
salt
nad
nadh
weight
Prior art date
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PCT/JP2006/300049
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English (en)
Japanese (ja)
Inventor
Toshikazu Kamiya
Masao Kimura
Yasushi Sakai
Original Assignee
Kyowa Hakko Kogyo Co., Ltd.
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Filing date
Publication date
Application filed by Kyowa Hakko Kogyo Co., Ltd. filed Critical Kyowa Hakko Kogyo Co., Ltd.
Priority to JP2006550895A priority Critical patent/JPWO2006073162A1/ja
Publication of WO2006073162A1 publication Critical patent/WO2006073162A1/fr

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Classifications

    • 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
    • A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to reduced nicotinamide adenine dinucleotide (hereinafter abbreviated as NADH) or reduced nicotinamide adenine dinucleotide phosphate (hereinafter, NADH and NADPH are combined.
  • NADH reduced nicotinamide adenine dinucleotide
  • NADPH reduced nicotinamide adenine dinucleotide phosphate
  • NAD (P) H is known to be effective for hypertension, Parkinson's disease, and the like, and preparations containing NAD (P) H for the prevention or treatment of these are also known.
  • NAD (P) H is unstable at room temperature, and there is a problem that the residual ratio decreases during storage as a preparation, that is, storage stability is not good. For this reason, normally, when formulating, a device for improving storage stability is performed.
  • Patent Document 1 See Patent Document 2), etc. are known! /, But an inexpensive method suitable for industrial use is desired.
  • Cyclodextrin is known as a compound having a structure in which glucose is bound cyclically, and consists of 6, 7, 8 and 9 glucoses, a-cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin and ⁇ - Cyclodextrins are well known. Various cyclodextrin derivatives are also known.
  • cyclodextrins and derivatives thereof have a cyclic structure, they have a cavity in the molecule, and the substance is taken into this cavity (generally called inclusion) It is known to make various substances soluble or stable. For example, it is known that ⁇ -cyclodextrin can stabilize vitamin B1 in an internal solution (see Patent Document 3). However, in order to stabilize a substance with cyclodextrin, it is necessary to dissolve cyclodextrin and the target substance in a solvent and bring them into contact for inclusion. There is a point.
  • Patent Document 1 U.S. Pat.No. 5,332,727
  • Patent Document 2 International Publication No. 2004Z050099 Pamphlet
  • Patent Document 3 Japanese Patent Laid-Open No. 2003-146880
  • An object of the present invention is to provide a method for improving the storage stability of NAD (P) H or a salt thereof, a solid composition containing NAD (P) H or a salt thereof with good storage stability, or a method for producing the same. There is.
  • the present invention relates to the following (1) to (5).
  • a method for improving the storage stability of NAD (P) H or a salt thereof comprising coexisting NAD (P) H or a salt thereof and cyclodextrin or a cyclodextrin derivative without dissolving them in a solvent.
  • a solid composition comprising NAD (P) H or a salt thereof and cyclodextrin or a cyclodextrin derivative.
  • a solid preparation comprising NAD (P) H or a salt thereof and cyclodextrin or a cyclodextrin derivative.
  • the present invention can provide a method for improving the storage stability of NAD (P) H or a salt thereof. Further, it is possible to provide a solid composition containing NAD (P) H or a salt thereof having good storage stability or a method for producing the same.
  • NAD (P) H or a salt thereof may be a natural product, a product obtained by using a microorganism or a processed product thereof, a product obtained by a chemical synthesis method, a purified product, or a crude product. Good. Commercially available products can also be used.
  • the salt of NAD (P) H may be any salt as long as it is a pharmacologically acceptable salt.
  • Alkali metal salts such as sodium salt and potassium salt, hydrochloride, sulfate, phosphate and the like
  • Organic acid salts such as inorganic acid salts, acetates, maleates, fumarate, citrates, lactates and methanesulfonates.
  • NAD (P) H or a salt thereof can be used in powders, granules and powders!
  • the cyclodextrin or cyclodextrin derivative may be any of those obtained from nature, those obtained by using microorganisms or processed products thereof, those obtained by chemical synthesis, and may be purified products or crude products. Commercially available products can also be used.
  • cyclodextrins include at-cyclodextrin, 13-cyclodextrin, maltosyl 13-cyclodextrin, ⁇ -cyclodextrin, and ⁇ -cyclodextrin.
  • the cyclodextrin derivative is not particularly limited as long as it is a cyclodextrin derivative having a cyclodextrin skeleton, and examples thereof include the derivatives described in WO98 / 55148.
  • hydroxyl groups of cyclodextrin is substituted with hydrogen, alkyl, hydroxyalkyl, carboxyalkyl, carboxyalkoxyalkyl, alkylcarbonylalkyl, alkoxycarbonylalkyl or hydroxyalkoxyalkyl. Derivatives and the like.
  • the alkyl moiety of the alkyl and alkoxy is preferably an alkyl having 1 to 6 carbon atoms, such as methyl, ethyl, 1-methylethyl, 1,1-dimethylethyl, propyl, 2-methylpropyl, butyl, pentyl, hexyl and the like. .
  • Examples of the cyclodextrin derivative include polyethers described in US Pat. No. 3,459,313.
  • the hydrogen power of one or more hydroxyl groups of cyclodextrin C1-C6 alkyl, hydroxylated C1-C6 alkyl, carboxylated C1-C6 alkyl or C1-C6 Substituted with an alkyloxycarbonylated alkyl group having 1 to 6 carbon atoms !, ethers, or mixed ethers thereof, preferably alkyls having 1 to 3 carbon atoms, hydroxyl groups.
  • Examples of the cyclodextrin derivative include sulfobutylcyclodextrin (US Pat. No. 5,134,127).
  • ⁇ -cyclodextrin ⁇
  • Cyclodextrin maltosyl ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, methyl 13-cyclodextrin, monochlorotriazyl 1 ⁇ -cyclodextrin, hydroxypropyl 1 ⁇ -cyclodextrin or triacetyl 1 ⁇ -cyclodextrin
  • A-cyclodextrin, j8-cyclodextrin, ⁇ -cyclodextrin or ⁇ -cyclodextrin is more preferable.
  • the cyclodextrin or cyclodextrin derivative may be used alone! However, it is possible to use a combination of two or more cyclodextrins or cyclodextrin derivatives.
  • Cyclodextrin or cyclodextrin derivatives can be used in the form of powder, granules and granules. Low moisture content!
  • the moisture content is preferably as low as possible, but is preferably 2% by weight or less, more preferably 1% by weight or less, and particularly preferably 0.5% by weight or less.
  • the water content exceeds 3% by weight, it is preferable to dry the cyclodextrin or cyclodextrin derivative so as to achieve the above water content.
  • drying method can dry the cyclodextrin or the cyclodextrin derivative, for example, natural drying, hot air drying, ventilation drying, air drying, spray drying, vacuum drying, Any method such as sun drying or vacuum drying may be used.
  • Specific methods include shelf drying, fluidized bed drying, and the like.
  • NAD (P) H or a salt thereof can be improved by allowing NAD (P) H or a salt thereof and cyclodextrin or a cyclodextrin derivative to coexist without dissolving in a solvent.
  • NAD (P) H or its salt and cyclodextrin or cyclodextrin derivative should be present.
  • NAD (P) H or a salt thereof and cyclodextrin or cyclodextrin derivative may be present as long as they can coexist without dissolving in the solvent.
  • Other solvents may also be present as long as they can coexist without dissolving in NAD (P) H or a salt thereof and cyclodextrin or cyclodextrin derivative.
  • NAD (P) H or a salt thereof and cyclodextrin or a cyclodextrin derivative to coexist without dissolving in a solvent
  • NAD (P) H or a salt thereof and cyclodextrin or cyclodextrin A method of mixing the derivative as it is without dissolving it in a solvent can be mentioned.
  • components that are usually used in the field of pharmaceuticals, foods, or feeds may be mixed so as not to adversely affect the storage stability of NAD (P) H.
  • the amount of cyclodextrin or cyclodextrin derivative coexisting with NAD (P) H or a salt thereof is not particularly limited, but is preferably 0.1 parts by weight or more per 1 part by weight of NAD (P) H or a salt thereof. More preferably, it is 1 part by weight or more, further preferably 10 parts by weight or more, and particularly preferably 20 parts by weight or more.
  • the storage stability of NAD (P) H or a salt thereof can be known as the residual ratio of NAD (P) H or a salt thereof after storing NAD (P) H or a salt thereof for a certain period.
  • the residual ratio of NAD (P) H or a salt thereof is, for example, the amount of NAD (P) H or a salt thereof before storage.
  • the amount of NAD (P) H or its salt (referred to as B) after storage (referred to as B) is quantified by a conventional method such as a method of measuring absorbance using a spectrophotometer, etc. The percentage can be calculated.
  • composition of the present invention is NAD (P) H when stored at 60 ° C for 14 days under shading conditions.
  • a composition with a residual ratio of 70% or more is preferred, and a composition with 75% or more is more preferred.
  • composition of the present invention may be in a crystalline, amorphous form as long as it is a solid composition containing NAD (P) H or a salt thereof and cyclodextrin or a cyclodextrin derivative. .
  • composition of the present invention comprises NAD (P) H or a salt thereof and a cyclodextrin or cyclodextrin derivative coexisting in a solvent without being dissolved, and if necessary mixed with components used in the pharmaceutical, food or food field. Can be prepared.
  • composition of the present invention can be used as a pharmaceutical, food or feed, but preferably used as a solid preparation together with a pharmaceutical base used in the pharmaceutical or food field.
  • solid preparations include tablets, capsules, suppositories, pills, powders, granules, etc.
  • Enteric tablets or enteric capsules that are preferred for tablets or capsules are available. Further preferred.
  • formulation base examples include excipients, disintegrants, binders, lubricants and the like.
  • excipients examples include maltose, trehalose, mannitol, reduced maltose starch syrup, lactitol, xylitol, sorbitol, erythritol, crystalline cellulose, low-substituted hydroxypropylcellulose, and the like.
  • the proportion of the excipient in the composition of the present invention is not particularly limited as long as it is within the range of general use in the preparation.
  • Examples of the disintegrant include carboxymethylcellulose, carboxymethylcellulose calcium, sodium carboxymethylcellulose, crospovidone, cros-noremerose sodium, sodium glycolate, corn starch, potato starch, and partial alpha starch starch.
  • examples include starch.
  • the proportion of the disintegrant in the composition of the present invention is not particularly limited as long as it is within the range of the general use in the preparation, but when the preparation is a tablet, 0 to 25% by weight is preferable. 0.01 to 20% by weight is more preferred 0.1 to 15% by weight is more preferred 1 to 10% by weight is particularly preferred.
  • binder examples include polybulurpyrrolidone, pullulan, methylcellulose, hydroxypropylcellulose, polybulal alcohol, gelatin, agar, pullulan and the like. Book The proportion of the binder in the composition of the invention is not particularly limited as long as it is within the range of general use in the formulation! ,.
  • the lubricant examples include sucrose fatty acid ester, stearic acid, magnesium stearate, calcium stearate, stearic acid metal salt such as sodium stearyl fumarate, daricelin fatty acid ester, hardened oil and fat, and the like.
  • the ratio of the lubricant in the composition of the present invention is not particularly limited as long as it is within the range of general use in the preparation.
  • the preparation is a tablet, 0 to 20% by weight is preferable. It is more preferably 0.01 to 10% by weight, and further preferably 0.05 to 5% by weight.
  • a sweetener In addition to the above-mentioned preparation base, a sweetener, a sour agent, a colorant, a fragrance, an antioxidant, a fluidizing agent and the like may be contained as necessary.
  • sweetening agent examples include saccharin sodium, glycyrrhizin dipotassium, aspartame, stevia, thaumatin, sucralose, glucose, funolectose, saccharose and the like.
  • the proportion of the sweetening agent in the composition of the present invention is not particularly limited as long as it is within the range of general use in the preparation.
  • Examples of the acidulant include citrate, tartaric acid, malic acid and the like.
  • the proportion of the sour agent in the composition of the present invention is not particularly limited as long as it is within the range of the general use amount in the preparation.
  • Examples of the colorant include food yellow No. 5, food red No. 2, food blue No. 2, and the like.
  • the proportion of the colorant in the composition of the present invention is not particularly limited as long as it is within the range of the general use amount in the preparation.
  • fragrances include lemon flavor, lemon lime flavor, grapefruit flavor, apple flavor and orange flavor.
  • proportion of the fragrance in the composition of the present invention is not particularly limited as long as it is within the range of general use in the preparation.
  • Antioxidants include tocopherol, cysteine hydrochloride, L-ascorbic acid stearate, and the like.
  • the proportion of the antioxidant in the composition of the present invention is not particularly limited as long as it is within the range of general use in the preparation.
  • Examples of the fluidizing agent include calcium phosphate, calcium hydrogen phosphate, fine particle nitric acid, etc. I can improve my strength.
  • the proportion of the fluidizing agent in the composition of the present invention is not particularly limited as long as it is within the range of general use in the preparation, but when the preparation is a tablet, 0 to 20% by weight is preferable. More preferred is 0.01 to 10% by weight, and more preferred is 0.05 to 5% by weight.
  • carbohydrates such as dextrin, niacin, vitamin E, vitamin C, vitamin B, vitamins such as vitamin A and vitamin D, minerals such as sodium, desiccant such as fine particulate nitric oxide, and key acid Anti-caking agents such as calcium, synthetic aluminum silicate and talc may be added.
  • the content of NAD (P) H or a salt thereof is preferably 0.01 to 90% by weight, more preferably 0.1 to 70% by weight, and further preferably 0.1 to 50% by weight. 1-30% by weight is particularly preferred.
  • the content of cyclodextrin or cyclodextrin derivative is preferably 10 to 99.99% by weight, more preferably 30 to 99.9% by weight, further preferably 50 to 99.9% by weight, and 70 to 70%. 99% by weight is particularly preferred U.
  • cyclodextrin or cyclodextrin derivative is contained per 1 part by weight of NAD (P) H. It is particularly preferable that it contains 1 part by weight or more, and more preferably 10 parts by weight or more, and even more preferably 20 parts by weight or more.
  • the tablet was obtained, for example, by mixing NAD (P) H or a salt thereof, cyclodextrin or cyclodextrin derivative and a pharmaceutical base, and if necessary, the above-mentioned components other than the pharmaceutical base.
  • Method of compression-molding the mixture (hereinafter referred to as direct compression method), NAD (P) H or its salt, cyclodextrin or cyclodextrin derivative and pharmaceutical base, and if necessary, the above components other than the pharmaceutical base
  • direct compression method NAD (P) H or its salt, cyclodextrin or cyclodextrin derivative and pharmaceutical base, and if necessary, the above components other than the pharmaceutical base
  • NAD (P) H or a salt thereof, cyclodextrin or cyclodextrin derivative and a pharmaceutical base and if necessary It can be produced by granulating and compressing all of the above components other than the base for use, but the direct tableting method is preferably used. I can.
  • Equipment used for compression molding is not particularly limited, and for example, a compressor such as a rotary compression molding machine or a hydraulic press machine can be used.
  • the surface of the tablets obtained by compression molding is used with a coating pan etc., and the bases usually used for mooncake coating such as shellac solution, twein solution, cenorelose acetate, etc. It can be manufactured by coating with.
  • a tablet when a tablet is produced as a sublingual tablet, it can be produced by tableting at a low pressure when tableting.
  • the hard capsule is an enteric-coated capsule
  • a base usually used for coating at the time of intestinal solvent production such as shellac solution, zein solution, cellulose acetate, etc. by a conventional method.
  • the dosage of the composition of the present invention varies depending on the purpose of administration, the mode of administration, the age, weight, symptoms, etc. of the human or non-human animal to be administered, such as human hypertension, Parkinson's disease, Alheimer's disease, etc.
  • 5 mg to 1500 mg, preferably 20 mg to 30 mg of NAD (P) H or a salt thereof is orally administered 1 to 3 times a day for each adult.
  • the dried cyclodextrin was dried at 105 ° C for 240 minutes using a constant temperature dryer, and the weight difference before and after drying was calculated.
  • the water content of cyclodextrin obtained by drying at 70 ° C was 0.28. %Met.
  • 96.6 g of the cyclodextrin and 3.4 g of NADH were mixed and stirred to obtain a mixed powder A.
  • D-mannthol (for oral use), manufactured by Nikken Kasei Co., Ltd.] was dried by the same method as cyclodextrin to obtain D-mannthol having a water content of 0.1%. Further, 96.6 g of the D-manntol and 3.4 g of NADH (manufactured by Kyowa Hakko Kogyo Co., Ltd.) were mixed and stirred to obtain a mixed powder B.
  • Mixed powder A and mixed powder B were each placed in a petri dish, the lid was shifted by half, and left in an incubator at 25 ° C. and a relative humidity of 43% for 5 hours. After standing, each powder was filled in an aluminum vapor deposition bag, sealed with a sealer, and stored at 60 ° C for 14 days.
  • the NADH content in the mixed powder after storage was quantified by the same method as before storage.
  • the mixed powder added with cyclodextrin had a residual ratio of NADH of 84% and was mixed with the mixed powder added with D-mannitol (mixed powder B).
  • the residual rate of NADH was 66%.
  • Mixed powder D was obtained using the same method as the production method of mixed powder C except that 2400 g of D-manntol prepared in Example 1 was used.
  • the mixed powders C and D were each tableted with a rotary tableting machine VIRG0524 (manufactured by Kikusui Seisakusho) to prepare about 300 mg of 9 mm ⁇ tablets C and D.
  • Tablets C and D were pulverized, and the obtained powder was used to measure the content of NADH in the tablet according to the method described in Example 1.
  • Tablets C and D were stored at 60 ° C for 14 days under light-shielded conditions, and the NADH content in the tablets was measured by the same method as before the storage.
  • the NADH residual rate after storage was calculated using the NADH content value in the tablet before and after storage, the NADH residual rate in tablet C containing cyclodextrin was 77%. On the other hand, the residual rate of NADH in tablet D containing D-mannitol was 69.
  • Example 2 The surface of tablet C prepared in Example 2 was coated with a shellac solution using Hicoater HCT-48 (Freund Sangyo Co., Ltd.) to produce an enteric tablet.
  • Hicoater HCT-48 Fraund Sangyo Co., Ltd.
  • a method for improving the storage stability of NAD (P) H or a salt thereof can be provided.
  • a solid composition containing NAD (P) H or a salt thereof having good storage stability or a method for producing the same can be provided.

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Abstract

La présente invention décrit une méthode d'amélioration de la stabilité au stockage de NADH ou de NADPH (l'abréviation 'NAD(P)H' sera employée par la suite pour désigner collectivement ces deux composés) ou d'un sel de l'un de ces composés. Ladite méthode est caractérisée en ce que NAD(P)H ou un sel correspondant est mis en présence de cyclodextrine ou d'un dérivé de cyclodextrine, sans dissoudre ces substances dans un solvant. La présente invention décrit également un procédé d'élaboration d'une préparation solide comprenant NAD(P)H ou un sel correspondant, associé à la cyclodextrine ou à un dérivé de cyclodextrine, ledit procédé comprenant le mélange de NAD(P)H ou d'un sel correspondant avec la cyclodextrine ou le dérivé de cyclodextrine sans dissoudre ces substances dans un solvant. La présente invention décrit en outre une préparation solide comprenant NAD(P)H ou un sel correspondant, associé à la cyclodextrine ou à un dérivé de cyclodextrine.
PCT/JP2006/300049 2005-01-07 2006-01-06 Methode d'amelioration de la stabilite au stockage du nadh ou du nadph ou d'un sel de ces composes WO2006073162A1 (fr)

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JP2006550895A JPWO2006073162A1 (ja) 2005-01-07 2006-01-06 Ｎａｄｈもしくはｎａｄｐｈまたはその塩の保存安定性向上方法

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6191125A (ja) * 1984-10-11 1986-05-09 Nippon Zeon Co Ltd Ｓ−アデノシル−ｌ−メチオニン含有組成物及びその製造法
JPS61212300A (ja) * 1985-03-15 1986-09-20 Unitika Ltd 保存安定性に優れたアルコ−ル検出用試験片
JPH01313000A (ja) * 1988-06-14 1989-12-18 Iatron Lab Inc 生体成分測定試薬
WO1994025007A1 (fr) * 1993-04-29 1994-11-10 Birkmayer U.S.A. Compositions therapeutiques perorales, stables et absorbables de nadh et de nadph
JPH09235302A (ja) * 1996-03-01 1997-09-09 Takeda Chem Ind Ltd 分岐シクロデキストリンカルボン酸エステルおよびその製造法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6191125A (ja) * 1984-10-11 1986-05-09 Nippon Zeon Co Ltd Ｓ−アデノシル−ｌ−メチオニン含有組成物及びその製造法
JPS61212300A (ja) * 1985-03-15 1986-09-20 Unitika Ltd 保存安定性に優れたアルコ−ル検出用試験片
JPH01313000A (ja) * 1988-06-14 1989-12-18 Iatron Lab Inc 生体成分測定試薬
WO1994025007A1 (fr) * 1993-04-29 1994-11-10 Birkmayer U.S.A. Compositions therapeutiques perorales, stables et absorbables de nadh et de nadph
JPH09235302A (ja) * 1996-03-01 1997-09-09 Takeda Chem Ind Ltd 分岐シクロデキストリンカルボン酸エステルおよびその製造法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SENO M. ET AL.: "Chromatographic behavior of cyclodextrin complexes of NADH and NADP", JOURNAL OF CHROMATOGRAPHY, vol. 508, no. 1, 1990, pages 127 - 132, XP003001304 *

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