WO2021078000A1 - Nadh 及其盐在制备防治咽炎的药物或保健食品中的应用 - Google Patents
Nadh 及其盐在制备防治咽炎的药物或保健食品中的应用 Download PDFInfo
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- WO2021078000A1 WO2021078000A1 PCT/CN2020/118817 CN2020118817W WO2021078000A1 WO 2021078000 A1 WO2021078000 A1 WO 2021078000A1 CN 2020118817 W CN2020118817 W CN 2020118817W WO 2021078000 A1 WO2021078000 A1 WO 2021078000A1
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- nadh
- preventing
- salt
- pharyngitis
- health food
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- 201000007100 Pharyngitis Diseases 0.000 title claims abstract description 25
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 235000013402 health food Nutrition 0.000 title claims abstract description 17
- 150000003839 salts Chemical class 0.000 title claims abstract description 16
- 229940079593 drug Drugs 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims abstract description 57
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims abstract description 56
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 9
- 210000003630 histaminocyte Anatomy 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 4
- 239000000427 antigen Substances 0.000 claims description 4
- 108091007433 antigens Proteins 0.000 claims description 4
- 102000036639 antigens Human genes 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 230000017531 blood circulation Effects 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 108010016731 PPAR gamma Proteins 0.000 claims description 2
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 claims description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 150000002978 peroxides Chemical class 0.000 claims description 2
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 230000019491 signal transduction Effects 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 claims 1
- 230000036737 immune function Effects 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000024891 symptom Diseases 0.000 abstract description 3
- 231100000957 no side effect Toxicity 0.000 abstract description 2
- 241000700159 Rattus Species 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 230000002000 scavenging effect Effects 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229940126678 chinese medicines Drugs 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 3
- 210000003800 pharynx Anatomy 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 2
- 108010021119 Trichosanthin Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229960003699 evans blue Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229940039009 isoproterenol Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229950006238 nadide Drugs 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 description 1
- ZRFWHHCXSSACAW-UHFFFAOYSA-M 3-morpholin-4-yloxadiazol-3-ium-5-amine;chloride Chemical compound [Cl-].O1C(N)=C[N+](N2CCOCC2)=N1 ZRFWHHCXSSACAW-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010013789 Dry throat Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 208000006735 Periostitis Diseases 0.000 description 1
- 230000002292 Radical scavenging effect Effects 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038776 Retching Diseases 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007108 local immune response Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 210000003460 periosteum Anatomy 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- CMFNMSMUKZHDEY-UHFFFAOYSA-M peroxynitrite Chemical compound [O-]ON=O CMFNMSMUKZHDEY-UHFFFAOYSA-M 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- Anti-inflammatory drugs have quick effects, but are prone to drug resistance, are difficult to cure, and cause damage to the stomach, intestines, liver, and kidneys.
- Traditional Chinese medicine tastes bad and it is inconvenient to take.
- proprietary Chinese medicine is convenient to take, the bioavailability of the drug is not high and the curative effect is not obvious.
- the toxic and side effects of many Chinese medicines and proprietary Chinese medicines on the human body are not clear, and long-term use is prone to side effects and resistance. Medicinal properties.
- the single dose of NADH during enteral administration is 0.1-10 mg/kg, preferably 0.1-4 mg/kg.
- the daily frequency is 1 to 3 times, and the daily dosage is 0.1 to 30 mg/kg, preferably 0.1 to 12 mg/kg, more preferably 0.4 to 2 mg/kg.
- the single dose of NADH for parenteral administration is 0.1 to 2 mg/kg, preferably 0.1 to 1 mg/kg. Wherein kg is the weight unit of the subject.
- the above-mentioned pharmaceutical composition is prepared by mixing NADH and its salt with conventional pharmaceutical excipients and preparing various dosage forms by conventional methods.
- the third technical purpose of this application is to provide a health food composition for preventing and treating pharyngitis, in which NADH and/or its pharmacologically acceptable salt are the only active ingredients.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Otolaryngology (AREA)
- Toxicology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种NADH及其盐在制备防治咽炎的药物或保健食品中的应用。NADH及其药理学上可接受的盐可用于制备防治咽炎的药物或保健食品。其将NADH或其盐作为唯一活性成分，给药方式多样，方便使用，可依据病情的严重程度决定施药途径和用药剂量，炎症症状有明显改善，基本不会引起副作用，复发率降低。
Description
本申请涉及药物或保健食品技术领域，尤其涉及NADH在制备防治咽炎的药物或保健食品中的应用。
咽炎是一种常见病，上呼吸道的炎症，很难根治，尤其是慢性咽炎，经常复发，其表现为咽喉有异物感、恶心干呕、咽喉干燥等症状，影响人们正常的工作和生活。慢性咽炎的发病机理概括起来有以下几点：①咽部有细菌和病毒等病原微生物的感染；②机体抵抗力下降，综合调节能力下降；③咽部结缔组织增生，粘膜和末梢神经处于高敏感状态；④咽部血管通透性增加，血管内皮细胞肿胀，管腔狭窄，血流不畅；⑤局部免疫反应失调，肥大细胞反应性增强，局部免疫复合物大量生成。
目前市场上治疗慢性咽炎的药品很多，主要以消炎药、中药和中成药为主。消炎药见效快，但容易产生抗药性，较难根治，且对胃、肠、肝、肾有损害。中药口感不好，且服用不方便，而中成药虽然服用方便，但是药物生物利用度不高，疗效不明显，而且很多中药和中成药对人体毒副作用尚不明确，长期服用易产生副作用和抗药性。
鉴于上述问题，本申请的技术目的之一在于提供NADH及其盐在制备防治咽炎的药物或保健食品中的应用。
在本申请中，所述NADH尤其指β-NADH，还原型烟酰胺腺嘌呤二核苷酸（Nicotinamide adenine dinucleotide）。
在本申请的其中一个实施例中，所述咽炎尤其指慢性咽炎。
在本申请的其中一个实施例中，所述NADH及其盐为肠内给药或肠外给药均可，其中更优选为口服给药、注射给药和吸入给药。
在本申请的其中一个实施例中，肠内给药时NADH的单次剂量为0.1~10mg/kg，优选为0.1~4mg/kg。日次数为1~3次，日用量为0.1~30mg/kg，优选是0.1~12mg/kg，更优选0.4~2mg/kg。肠外给药时NADH的单次剂量为0.1~2mg/kg，优选是0.1~1mg/kg。其中kg为对象个体的体重单位。
在本申请的其中一个实施例中，使用NADH及其盐时将其与辅料混合制成不同的剂型，包括但不限于片剂、粉剂、胶囊剂、颗粒剂、丸剂、混悬剂、糖浆剂、合剂、散剂、滴丸、注射剂、软膏剂、栓剂、吸入剂中的任意一种。
本申请中NADH用于制备防治咽炎的药物或保健食品，首先，NADH具有强抗氧化性，能够清除羟自由基和过氧化硝酸阴离子，抑制NF-κB信号通路的激活和COX-2的表达，激活PPAR-γ的表达，进而阻止咽炎相关基因的转录和表达，改善炎症状态，特别是NADH的氢离子具有强的选择性抗氧化作用，能够只与•OH 和ONOO－发生反应，并不与其它在生理过程中发挥作用的活性氧(如O2•
－、H
2O
2和NO•等)反应；其次，NADH能够调节免疫能力，能显著抑制肥大细胞在抗原攻击下脱颗粒反应，增强清除血循环内免疫复合物能力。
本申请的技术目的之二在于提供一种防治咽炎的药物组合物，所述药物组合物中以NADH和/或其药理学上可接受的盐为唯一活性成分。
在本申请的其中一个实施例中，上述药物组合物还包括药学上可接受的辅料。
在本申请的其中一个实施例中，上述药物组合物是将NADH及其盐与常规的药用辅料混合，以常规的方法制成各种剂型。
在本申请的其中一个实施例中，上述药物组合物的给药方式优选为口服给药、注射给药或吸入给药。
本申请的技术目的之三在于提供一种防治咽炎的保健食品组合物，所述保健食品组合物中以NADH和/或其药理学上可接受的盐为唯一活性成分。
在本申请的其中一个实施例中，上述保健食品组合物还包括食品中可接受的辅料。
在本申请的其中一个实施例中，上述保健食品组合物的给药方式为口服给药、注射给药或吸入给药。
实施本申请实施例，将具有如下有益效果：
本申请依据NADH的特性，公开了其应用于制备防治咽炎尤其是慢性咽炎药物或保健食品中的应用，将NADH和/或其盐作为唯一活性成分，其给药方式多样，方便使用，可依据病情的严重程度决定施药途径和用药剂量，炎症症状有明显改善，基本不会引起副作用，复发率降低，是一种值得推广的药物或保健食品。
下面将结合具体实施例对本申请的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
实施例1
NADH对大鼠颅骨骨膜肥大细胞脱颗粒反应的影响：
取Wistar大鼠50只，随机分为5组，即对照1组、对照2组，实验1组、实验2组和实验3组。各组每只大鼠每天分别以注射的给药方式给予生理盐水10mL、异丙肾上腺素10mg/kg、NADH 5mg/kg、NADH 10mg/kg和NADH 15mg/kg，每日1次，连续30天，末次给药后，将大鼠给予抗天花粉蛋白抗血清0.1mL、天花粉Evans蓝溶液(天花粉蛋白1mg溶于1mL0.5％Evans蓝溶液)，两溶液的重量比例为1:20，经静脉注射，30分钟后，处死大鼠，立即剪下颅骨，显微镜下观察计数，计算肥大细胞脱颗粒的百分率，结果见表1。
以上实验数据表明：NADH能够抑制抗原引起的大鼠肥大细胞脱颗粒反应，显著低于生理盐水对照1组的肥大细胞脱颗粒百分率，尤其是实验3组与异丙肾上腺素的抑制程度相当。说明本申请中的NADH对抗原引起的大鼠肥大细胞脱颗粒反应有较好的疗效。
实施例2
NADH在体外对羟基自由基(•OH)的清除效果：
依据的原理：采用邻二氮菲-金属离子-H
2O
2，通过Fenton反应(H
2O
2+Fe
2+→•OH+H
2O+Fe
3+)生成羟自由基(•OH)，促使邻二氮菲-Fe
2+被氧化为邻二氮菲-Fe
3+，造成其水溶液在波长440nm处最大消失，来测算其清除率。
具体步骤是:48孔板中的孔分成4组，分别为对照组，实验1组、实验2组和实验3组，每组的每个孔中分别加入300μL双蒸水、0.1μM的NADH、0.5μM的NADH和1.0μM的NADH(用水溶解)，加入50μL 1.0mM邻二氮菲(配制1.0mM溶解于50mM NaCl溶液)，然后分别加入125μL 1.0mM H
2O
2和125μL 2.0mM Fe
2+混匀，用BioTek Synergy HT酶标仪测定100秒内在440nm波长处吸光值减少百分率。羟基自由基清除率计算公式为：清除率(％)＝[1－(A
0－A
100)/A
0]×100％，A
0和A
100分别为在0秒和100秒时的吸光值，数据见表2。
实施例3
NADH在体外对过氧化硝酸阴离子（ONOO
－）的清除效果：
依据的原理：SIN-1在弱碱性条件下(PBS pH 7.4)分解，能够同时产生超氧阴离子自由基(O
2-•)以及一氧化氮自由基(NO•)，二者瞬间再产生过氧亚硝基阴离子(ONOO
-)。ONOO
-与鲁米诺反应，使其氧化激发，发射425nm波长的光。
实验操作具体步骤为：先使用微量移液器在96孔黑底不透明酶标板中的每个孔中加入60μL 0.1mol/L PBS(pH＝7.4)溶液，将孔分成4组，分别为对照组，实验1组、实验2组和实验3组，每个组的每个孔中分别加入100μL 0.1mol/L PBS(pH＝7.4)溶液、100μL0.1μM NADH、100μL0.5μM NADH和100μL1.0μM NADH，其中NADH用水溶解配成溶液，再使用加液器在孔模式下向每个孔中分别加20μL 1.0mmol/L Luminol溶液和20μL 3mg/mL
SIN-1hydrochloride溶液，动力学模式总时间00：33：20，时间间隔为00：01：40。测定发光强度判断ONOO-的产生，抗氧剂(AH)与鲁米诺(L)竞争与ONOO
-反应，减少了ONOO
-与LH
-的反应，降低了发光强度。其发光强度与抗氧剂的抗氧化能力呈负相关，在化学发光仪上每隔一段时间记录发光强度，使用清除率来描述抗氧剂捕获ONOO
-的能力。清除率(％)＝(A
ctrl－A
sample)/A
ctrl×100％。其中，(A
ctrl为对照组的发光强度，A
sample为实验组的发光强度。
对过氧化硝酸阴离子(ONOO
-)的清除作用的效果数据如表3所示。
从表2和表3可以看出，与对照组相比，NADH对羟基自由基(•OH)，过氧化硝酸阴离子(ONOO
-)的清除作用比对照组都要高，尤其是1.0μM NADH组效果更好。
实验例4
NADH对大鼠慢性咽喉炎影响：
SD大鼠40只，体重200～220g，每日喷70％浓氨水，连续30天，建立慢性咽喉炎模型，然后按体重随机分为4组，每组10只，即：模型组、实验1组、实验2组、实验3组，另取10只正常SD大鼠作为对照组。模型组、实验1组、实验2组、实验3组和对照组，每日每组大鼠分别给药：相当量的水、NADH 5mg/kg，NADH 10mg/kg、NADH 15mg/kg和相当量的水，1次/日，连续30天。末次给药后用3％戊巴比妥钠腹腔麻醉安乐死，取血进行白细胞、粒细胞数检测。
如表4所示，与对照组相比，模型组白细胞和粒细胞数目显著升高(P＜0.01)；而实验组使用NADH后可使其数目降低，与模型组比较具有显著性差异(P＜0.01)，证明NADH对慢性咽炎具有明显改善作用。
以上所揭露的仅为本申请较佳实施例而已，当然不能以此来限定本申请之权利范围，因此依本申请权利要求所作的等同变化，仍属本申请所涵盖的范围。
Claims (10)
- NADH及其盐在制备防治咽炎的药物或保健食品中的应用。
- 根据权利要求1所述的应用，其特征在于，所述NADH为还原型烟酰胺腺嘌呤二核苷酸。
- 根据权利要求1所述的应用，其特征在于，所述NADH及其盐为口服给药、注射给药或吸入给药。
- 根据权利要求3所述的应用，其特征在于，口服给药时NADH的单次剂量为0.1~10mg/kg，注射给药和吸入给药时NADH的单次剂量为0.1~2mg/kg，每日给药1~3次。
- 根据权利要求4所述的应用，其特征在于，所述NADH用于制备防治咽炎的药物或保健食品是基于NADH能够增强人体内NAD+和氢离子水平，具有强抗氧化性，能够清除羟自由基和过氧化硝酸阴离子，抑制NF-κB信号通路的激活和COX-2的表达，激活PPAR-γ的表达，进而阻止咽炎相关基因的转录和表达，改善炎症状态；并且NADH能够调节免疫能力，能显著抑制肥大细胞在抗原攻击下脱颗粒反应，增强清除血循环内免疫复合物能力。
- 根据权利要求1所述的应用，其特征在于，使用NADH及其盐时将其与辅料混合制成不同的剂型，选自片剂、粉剂、胶囊剂、颗粒剂、丸剂、混悬剂、糖浆剂、合剂、散剂、滴丸、注射剂、软膏剂、栓剂和吸入剂中的任意一种。
- 一种防治咽炎的药物组合物，其特征在于，所述药物组合物以NADH和/或其药理学上可接受的盐为唯一活性组分。
- 据权利要求7所述的药物组合物，其特征在于，其还包括药学上可接受的辅料。
- 一种防治咽炎的保健食品组合物，其特征在于，所述保健食品组合物以NADH和/或其药理学上可接受的盐为唯一活性组分。
- 根据权利要求9所述的保健食品组合物，其特征在于，其还包括食品中可接受的辅料。
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| CN201911016534.2 | 2019-10-24 |
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