CN114983950A - Nicotinoyl nucleotide disintegrating tablet - Google Patents
Nicotinoyl nucleotide disintegrating tablet Download PDFInfo
- Publication number
- CN114983950A CN114983950A CN202110222605.5A CN202110222605A CN114983950A CN 114983950 A CN114983950 A CN 114983950A CN 202110222605 A CN202110222605 A CN 202110222605A CN 114983950 A CN114983950 A CN 114983950A
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- China
- Prior art keywords
- gelatin
- beta
- nicotinamide mononucleotide
- orally disintegrating
- disintegrating tablet
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- 239000002773 nucleotide Substances 0.000 title description 3
- FZAQROFXYZPAKI-UHFFFAOYSA-N anthracene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC3=CC(S(=O)(=O)Cl)=CC=C3C=C21 FZAQROFXYZPAKI-UHFFFAOYSA-N 0.000 claims abstract description 74
- 239000006191 orally-disintegrating tablet Substances 0.000 claims abstract description 53
- 108010010803 Gelatin Proteins 0.000 claims abstract description 48
- 239000008273 gelatin Substances 0.000 claims abstract description 48
- 229920000159 gelatin Polymers 0.000 claims abstract description 48
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- 239000003826 tablet Substances 0.000 claims description 32
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- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
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- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
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- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 240000008415 Lactuca sativa Species 0.000 description 1
- 235000003228 Lactuca sativa Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
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- 229940125396 insulin Drugs 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
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- 239000000594 mannitol Substances 0.000 description 1
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- 238000004519 manufacturing process Methods 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
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- 229960001462 sodium cyclamate Drugs 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2063—Proteins, e.g. gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
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- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an orally disintegrating tablet containing large-size beta-nicotinamide mononucleotide and a preparation method thereof. The orally disintegrating tablet contains beta-nicotinamide mononucleotide and gelatin as active components. The invention further relates to a specific dosage of gelatin as a delivery system, so that a large-size beta-nicotinamide mononucleotide orally disintegrating tablet can be prepared.
Description
Technical Field
The invention relates to an orally disintegrating tablet containing large-size beta-nicotinamide mononucleotide and a preparation method thereof. The orally disintegrating tablet contains beta-nicotinamide mononucleotide as an active ingredient and gelatin, but does not contain a conventional freeze-dried proppant. The invention further relates to gelatin as a delivery system to prepare large-format orally disintegrating tablets of beta-nicotinamide mononucleotide.
Background
Beta-nicotinamide mononucleotide, abbreviated NMN, CAS number: 1094-61-7, is a naturally occurring biologically active nucleotide. The researches of various periodicals such as Nature, Science, Cell and the like show that the beta-nicotinamide mononucleotide has the effects of delaying, improving and preventing aging and has important influence on the health of human bodies.
Some researches show that the beta-Nicotinamide Mononucleotide (NMN) has a regulating effect on the secretion of insulin, can intervene and treat type 2 diabetes, has a protection effect on acute kidney injury, has an auxiliary treatment effect on cancer, and has the effects of dispelling the effects of alcohol, protecting the liver, protecting eyesight, hearing and the like.
The currently marketed beta-nicotinamide mononucleotide preparations are mainly capsules and tablets.
However, due to the limitation of dosage forms, common tablets or capsules have slow effect after being taken, are difficult to take without water, and have low compliance of users. Moreover, because the existing beta-nicotinamide mononucleotide preparation is prepared by a conventional solid preparation process, the heating condition can occur in the process of the process regardless of a dry method and a wet method, the stability of the beta-nicotinamide mononucleotide is damaged, and the content loss is easy to occur.
Patent CN202010811659.0 discloses a β -nicotinamide mononucleotide capsule, which is prepared by taking β -nicotinamide mononucleotide as a raw material, starch, sodium carboxymethyl starch, silicon dioxide, lactose and magnesium stearate as auxiliary materials and adopting a premixing hybridization-total mixing-capsule filling process. The beta-nicotinamide mononucleotide capsule is prepared by a conventional solid preparation process, and the prepared capsule has slow response and poor compliance.
The lyophilized orally disintegrating tablets on the market generally have a small carrier dose of the water-soluble drug. Due to insufficient freezing process, water-soluble drugs may form eutectic mixtures, and there is a possibility that the removal of ice crystal support structures upon melting or drying at elevated temperatures may result in collapse of various forms, affecting quality indices such as molded appearance, disintegration, dissolution, product stability, and the like. In addition, when the product with overlarge single dose is prepared into the oral fast disintegrating tablet, the tablet is overweight and overlarge, so that the patient feels fear and is not favorable to take the product.
The large-dose freeze-dried orally disintegrating tablet is not favorable for sublimation of water in the freeze-drying process due to high solid content, and the freeze-dried tablet is compact and has less pores, so that the large-dose freeze-dried orally disintegrating tablet is not favorable for quick release of the freeze-dried orally disintegrating tablet. And when a conventional freeze-drying process is adopted and a conventional propping agent such as sugar alcohol or sugar is added, the prepared large-dose orally disintegrating tablet has the problems that more cracks appear on the surface of the disintegrating tablet, yellow spots appear on the surface of the disintegrating tablet, the bottom of the orally disintegrating tablet is stuck, and granular substances are slightly arranged at the bottom of the orally disintegrating tablet, so that the actual use requirement cannot be met.
Theoretically, the maximum unit dose of the freeze-dried orally disintegrating tablet prepared from the water-soluble drugs is 60mg, and the dose of the variety actually on the market is mostly within 10 mg.
The beta-nicotinamide mononucleotide which is used as a water-soluble substance shows certain viscosity in water, the higher the concentration is, the higher the viscosity is, the eutectic point is prolonged, and the freeze-drying and forming are difficult to realize.
Therefore, it is highly desirable to find a product that is an orally disintegrating tablet of β -nicotinamide mononucleotide in large size (or in large unit dose size) and that can meet the requirements of practical use.
Disclosure of Invention
The invention aims to develop a large-specification beta-nicotinamide mononucleotide orally disintegrating tablet with unit dose, improve the compliance of a beta-nicotinamide mononucleotide user and meet the requirement of practical use, for example, the obtained large-specification beta-nicotinamide mononucleotide orally disintegrating tablet does not have more cracks on the surface, does not have yellow spots on the surface, does not have bottom sticking phenomenon at the bottom of the orally disintegrating tablet, does not have granular substances at the bottom, and the like. The inventor finds that when a specific amount of gelatin is used for the orally disintegrating tablet of the large-specification beta-nicotinamide mononucleotide, the beta-nicotinamide mononucleotide quick-release preparation with the large-specification unit dose can be obtained, the practical use requirement is met, and the phenomenon of influencing the product stability is avoided. The object of the invention is thus achieved.
The invention relates to a large-specification beta-nicotinamide mononucleotide-containing orally disintegrating tablet, which contains beta-nicotinamide mononucleotide and 2-8.5% (by mass) of gelatin and does not contain a proppant for freeze drying, wherein the large specification refers to that the amount of the beta-nicotinamide mononucleotide in the orally disintegrating tablet in unit dose of the beta-nicotinamide mononucleotide is more than 60mg and less than 200 mg.
The second aspect of the invention relates to gelatin for a large-size beta-nicotinamide mononucleotide orally disintegrating tablet, wherein the content of the gelatin in the orally disintegrating tablet is 2-8.5% (by mass), and the large size refers to that the amount of the beta-nicotinamide mononucleotide in the orally disintegrating tablet in a unit dose of the beta-nicotinamide mononucleotide is more than 60mg and less than 200 mg.
The invention also relates to application of gelatin in preparation of large-size beta-nicotinamide mononucleotide orally disintegrating tablets, wherein the large size is that the amount of beta-nicotinamide mononucleotide in the orally disintegrating tablets is more than 60mg and less than 200mg in unit dose of beta-nicotinamide mononucleotide.
Still another aspect of the present invention relates to a method for preparing a rapid release formulation of beta-nicotinamide mononucleotide, comprising:
1. dissolving gelatin to generate gelatin water solution,
2. adding beta-nicotinamide mononucleotide into the aqueous solution in the step 1,
3. freeze drying the solution in 2.
Description of the terms
According to the present invention, the term "large format" is used to mean that the amount of β -nicotinamide mononucleotide in a unit dose thereof is greater than 60mg, preferably greater than 60mg, less than 200mg, more preferably: 75-150 mg.
According to the present invention, "unit dose" is generally understood by those of ordinary skill in the art of pharmaceutical manufacture, as for tablets, to refer to the amount of active ingredient in each tablet or tablet.
According to the invention, a "large format unit dose" is the amount of β -nicotinamide mononucleotide in a unit dose: greater than 60mg, less than 200mg, preferably: 75-150 mg.
According to the invention, the gelatin of the invention can be used as a freeze-drying binder, such as: cow leather gelatin, fish skin gelatin, cow bone gelatin, pig bone gelatin, and fish bone gelatin.
According to the invention, the freeze-drying proppant is a freeze-drying proppant commonly used in the field, such as sugar or sugar alcohol freeze-drying proppant, for example, mannitol, dextran, lactose, trehalose, povidone, sorbitol, amino acid, pullulan and the like.
Description
According to the invention, when the gelatin is used, the gelatin is firstly heated or dissolved in water by warm water or hot water, and the concentration of the gelatin in the water solution is 0.4-1.9%, and the preferable use concentration is 0.7-1.6%. Specifically, the content range of gelatin in the unit dose orally disintegrating tablet is 2.0 mg-9.25 mg/tablet. The content range of the gelatin is preferably 3.5 mg-8.0 mg/tablet.
According to the present invention, the orally disintegrating formulation of the present invention may further contain a flavoring agent in an amount of preferably 0.05mg to 0.5mg per tablet, as the case requires. Examples of corrigents are: such as aspartame, saccharin sodium, sodium cyclamate, sucralose, etc.
According to the invention, the preparation method of the beta-nicotinamide mononucleotide quick-release preparation comprises the following steps: dissolving gelatin in warm or hot water, cooling the gelatin water solution to room temperature, and adding beta-nicotinamide mononucleotide and corrective to dissolve completely. The solution is quickly packed into a sheet-shaped mould, frozen at low temperature, put into a vacuum state and freeze-dried.
The following examples are further illustrative of the present invention, but are not meant to limit the invention in any way.
Example 1
100mg beta-nicotinamide mononucleotide orally disintegrating tablet and its physical and chemical properties
| Disintegrating tablet component | Preparation amount | Unit dose |
| Beta-nicotinamide mononucleotide | 20g | 100mg |
| Gelatin | 0.9g | 4.5mg |
| Aspartame | 0.03g | 0.15mg |
| Water (sublimation) | Adding to 100ml | —— |
Preparation:
1. measuring about 80ml of water for later use, adding gelatin with the prescription amount, stirring in a water bath at 60 ℃ until the gelatin is completely dissolved, and cooling to room temperature.
2. Weighing the aspartame and the beta-nicotinamide mononucleotide in the formula amount, adding the aspartame and the beta-nicotinamide mononucleotide into the solution obtained in the step (1), and stirring until the aspartame and the beta-nicotinamide mononucleotide are completely dissolved and clear. Adding water to 100ml, and stirring.
3. The solution was added to the blister in 0.5ml per tablet.
4. Prefreezing to completion at-55 deg.C, and vacuumizing to 0.15 mbar.
5. Heating to-35 deg.C at a rate of 1 deg.C/4 min, holding at-35 deg.C for 200 min, heating to-15 deg.C at a rate of 1 deg.C/4 min, holding at-15 deg.C for 90 min, heating to 0 deg.C at a rate of 1 deg.C/min, and holding at 0 deg.C for 30 min.
6. The temperature is raised to 20 ℃ at a speed of 1 ℃/min, the temperature is maintained for 30 minutes at 20 ℃, the temperature is raised to 35 ℃ again at a speed of 1 ℃/min, and the temperature is maintained for 20 minutes at 35 ℃.
The total dosage of the oral disintegrating tablet is 200 tablets of beta-nicotinamide mononucleotide oral disintegrating tablets, and the specification is 100 mg/tablet.
Physical and chemical properties: the obtained beta-nicotinamide mononucleotide orally disintegrating tablet comprises the following components: the sheet is complete, the surface is smooth, and the phenomena of cracks and bottom sticking are avoided.
Comparative example 1
Orally disintegrating tablet containing 100mg beta-nicotinamide mononucleotide and no gelatin and its physical and chemical properties
| Disintegrating tablet component | Preparation amount | Unit dose |
| Beta-nicotinamide mononucleotide | 20g | 100mg |
| Sorbitol | 7g | 35mg |
| Aspartame | 0.03g | 0.15mg |
| Water (sublimation) | Adding to 100ml | —— |
Preparation:
1. approximately 80ml of water was measured for use.
2. Weighing sorbitol, aspartame and beta-nicotinamide mononucleotide according to the prescription amount, adding the sorbitol, aspartame and beta-nicotinamide mononucleotide into the solution obtained in the step (1), and stirring until the sorbitol, aspartame and beta-nicotinamide mononucleotide are completely dissolved and clear. Adding water to 100ml, and stirring.
3. The solution was added to the blister in 0.5ml per tablet.
4. Prefreezing to completion at-50 deg.C, and vacuumizing to 0.15 mbar.
5. Heating to-35 deg.C at a rate of 1 deg.C/4 min, holding at-35 deg.C for 120 min, heating to-15 deg.C at a rate of 1 deg.C/4 min, holding at-15 deg.C for 120 min, heating to 0 deg.C at a rate of 1 deg.C/2 min, and holding at 0 deg.C for 30 min.
6. The temperature is raised to 20 ℃ at the speed of 1 ℃/min, the temperature is maintained for 30 minutes at 20 ℃, the temperature is raised to 35 ℃ at the speed of 1 ℃/min, and the temperature is maintained for 20 minutes at 35 ℃.
The oral disintegrating tablet of 200 tablets of beta-nicotinamide mononucleotide is prepared, and the specification is 100 mg/tablet.
Physical and chemical properties: the obtained beta-nicotinamide mononucleotide orally disintegrating tablet comprises the following components: the tablet is complete, but more cracks appear on the surface, the yellow spot phenomenon appears on the surface, the bottom of the orally disintegrating tablet is sticky, and the bottom is slightly granular.
Example 2
Orally disintegrating unit-dose orally disintegrating tablet comprising 100mg of beta-nicotinamide mononucleotide and having different gelatin contents, and its physical and chemical properties
Unit dose
| Components | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 | Prescription 7 | Prescription 8 |
| Beta-nicotinamide mononucleotide | 100mg | 100mg | 100mg | 100mg | 100mg | 100mg | 100mg | 100mg |
| Gelatin | 1.75mg | 2mg | 3.5mg | 5mg | 6.5mg | 8mg | 9.25mg | 10mg |
| Aspartame | 0.15mg | 0.15mg | 0.15mg | 0.15mg | 0.15mg | 0.15mg | 0.15mg | 0.15mg |
Preparation and physical and chemical properties thereof:
1. measuring about 80ml of water for later use, adding gelatin with the prescription amount, stirring in a water bath at 60 ℃ until the gelatin is completely dissolved, and cooling to room temperature.
2. Weighing the aspartame and the beta-nicotinamide mononucleotide in the formula amount, adding the aspartame and the beta-nicotinamide mononucleotide into the solution obtained in the step (1), and stirring until the aspartame and the beta-nicotinamide mononucleotide are completely dissolved and clear. Adding water to 100ml, and stirring.
3. The solution was added to the blister in 0.5ml per tablet.
4. Prefreezing to completion at-55 deg.C, and vacuumizing to 0.15 mbar.
5. Heating to-35 deg.C at a rate of 1 deg.C/4 min, holding at-35 deg.C for 200 min, heating to-15 deg.C at a rate of 1 deg.C/4 min, holding at-15 deg.C for 90 min, heating to 0 deg.C at a rate of 1 deg.C/min, and holding at 0 deg.C for 30 min.
6. The temperature is raised to 20 ℃ at the speed of 1 ℃/min, the temperature is maintained for 30 minutes at 20 ℃, the temperature is raised to 35 ℃ at the speed of 1 ℃/min, and the temperature is maintained for 20 minutes at 35 ℃.
7. The above steps were repeated except that gelatin was added in different prescribed amounts to give 100mg/β -nicotinamide mononucleotide tablets of formulae 1-8.
Physical and chemical properties: the prescription 1 beta-nicotinamide mononucleotide orally disintegrating tablet is slightly loose and not dense, and is easy to crack when being taken.
The orally disintegrating tablet of 2-7 beta-nicotinamide mononucleotide in the prescription has complete tablet form, smooth surface and no crack and bottom sticking.
The 8 beta-nicotinamide mononucleotide orally disintegrating tablet of the prescription is complete, but the surface of the orally disintegrating tablet is cracked, and the bottom of the freeze-dried tablet is adhered to a bubble cap.
Example 3
Simulated mouth melting test of the product of example 1, comparative example 1 and commercial conventional formulation
The solubility test of the orally disintegrating tablet of β -nicotinamide mononucleotide was investigated to simulate its release in the oral cavity, according to USP standards.
Solubility test: the sample was placed in 2ml of water at 37 ℃ and the phenomenon was observed by standing.
Sample preparation: example 1 sample, comparative example 1 sample
Commercially available conventional formulations: the Golingwodel NMN9600 yeast extract composite powder is 133 mg/granule, and the auxiliary materials comprise yeast extract, broccoli seed water extract, avocado, carrot and lettuce.
| Sample (I) | Results of solubility or disintegration experiments | Remarks for note |
| Example 1 sample | Can be completely disintegrated and dispersed within 8s | The sheet is complete, the surface is smooth, and the phenomena of cracks and bottom sticking are avoided. |
| Comparative example 1 sample | Can be completely disintegrated and dispersed within 25s | The freeze-dried tablet has poor forming state and more cracks. |
| Conventional preparation on the market | Can be disintegrated in 25 minutes | And (4) capsules, wherein the content is brown powdery substance. |
The experimental data show that the beta-nicotinamide mononucleotide orally disintegrating tablet with specific gelatin content can achieve the quick release effect in a very short time, the forming state is good, the beta-nicotinamide mononucleotide orally disintegrating tablet without gelatin in the comparative example 1 is not good in forming state, and the disintegration time is relatively slow.
The conventional preparation on the market is a capsule, the content is brown powdery substance, and the disintegration is slow, and the disintegration lasts for about 25 minutes.
Claims (8)
1. An orally disintegrating tablet containing large-size beta-nicotinamide mononucleotide, which contains beta-nicotinamide mononucleotide and 2-8.5% (mass) gelatin, and does not contain a proppant for freeze-drying, wherein the large-size beta-nicotinamide mononucleotide in the orally disintegrating tablet of unit dose is more than 60mg and less than 200 mg.
2. The gelatin for the large-size beta-nicotinamide mononucleotide orally disintegrating tablet comprises 2-8.5% (by mass) of gelatin, a freeze-drying propping agent is not contained in the disintegrating tablet, and the large size is that the beta-nicotinamide mononucleotide in the orally disintegrating tablet with unit dose is more than 60mg and less than 200 mg.
3. The application of gelatin in preparing large-size beta-nicotinamide mononucleotide orally disintegrating tablets is that the gelatin is used in an amount of 2-8.5% (by mass), the orally disintegrating tablets do not contain a propping agent for freeze drying, and the large size refers to that the beta-nicotinamide mononucleotide in the orally disintegrating tablets with unit dose is more than 60mg and less than 200 mg.
4. The orally disintegrating tablet of claim 1, 2 or 3, further comprising a flavoring agent.
5. The orally disintegrating tablet of claim 4, wherein the flavoring agent is selected from aspartame.
6. An orally disintegrating tablet according to claim 1 or 2 or 3, wherein the gelatin is selected from the group consisting of bovine hide gelatin, fish skin gelatin, bovine bone gelatin, porcine bone gelatin and fishbone gelatin.
7. The orally disintegrating tablet of claim 1 or 2 or 3, wherein said orally disintegrating tablet is an orally disintegrating tablet having a unit dose of 100mg β -nicotinamide mononucleotide.
8. A method for preparing large-format beta-nicotinamide mononucleotide, comprising:
(1) dissolving gelatin to generate gelatin water solution,
(2) adding beta-nicotinamide mononucleotide into the aqueous solution in the step (1),
(3) and (3) freeze-drying the solution in the step (2).
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110222605.5A CN114983950A (en) | 2021-02-27 | 2021-02-27 | Nicotinoyl nucleotide disintegrating tablet |
| PCT/CN2022/078130 WO2022179634A1 (en) | 2021-02-27 | 2022-02-27 | Lyophilized oral preparation |
| PCT/CN2022/078131 WO2022179635A1 (en) | 2021-02-27 | 2022-02-27 | β-NICOTINAMIDE MONONUCLEOTIDE FREEZE-DRIED ORAL PREPARATION |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110222605.5A CN114983950A (en) | 2021-02-27 | 2021-02-27 | Nicotinoyl nucleotide disintegrating tablet |
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| CN114983950A true CN114983950A (en) | 2022-09-02 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015074587A1 (en) * | 2013-11-21 | 2015-05-28 | 李和伟 | Protective device for freeze-dried excipient preparation containing binder and preparation methods therefor |
| CN108853042A (en) * | 2018-09-20 | 2018-11-23 | 北京哈三联科技有限责任公司 | A kind of Mirtazapine freeze-drying oral disintegrating tablet and its preparation method and application |
| CN112137977A (en) * | 2020-09-28 | 2020-12-29 | 深圳雾件科技有限公司 | Nicotinamide mononucleotide sustained-release enteric orally disintegrating tablet and preparation method thereof |
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2021
- 2021-02-27 CN CN202110222605.5A patent/CN114983950A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015074587A1 (en) * | 2013-11-21 | 2015-05-28 | 李和伟 | Protective device for freeze-dried excipient preparation containing binder and preparation methods therefor |
| CN108853042A (en) * | 2018-09-20 | 2018-11-23 | 北京哈三联科技有限责任公司 | A kind of Mirtazapine freeze-drying oral disintegrating tablet and its preparation method and application |
| CN112137977A (en) * | 2020-09-28 | 2020-12-29 | 深圳雾件科技有限公司 | Nicotinamide mononucleotide sustained-release enteric orally disintegrating tablet and preparation method thereof |
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| 李聘等: "冻干型口崩片的研究进展", 《中国药师》, vol. 23, no. 11, 5 November 2020 (2020-11-05), pages 2253 - 2257 * |
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