CN112778092B - Reduced vitamin K 2 Preparation method and application thereof - Google Patents
Reduced vitamin K 2 Preparation method and application thereof Download PDFInfo
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- CN112778092B CN112778092B CN202011621712.7A CN202011621712A CN112778092B CN 112778092 B CN112778092 B CN 112778092B CN 202011621712 A CN202011621712 A CN 202011621712A CN 112778092 B CN112778092 B CN 112778092B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/06—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by conversion of non-aromatic six-membered rings or of such rings formed in situ into aromatic six-membered rings, e.g. by dehydrogenation
- C07C37/07—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by conversion of non-aromatic six-membered rings or of such rings formed in situ into aromatic six-membered rings, e.g. by dehydrogenation with simultaneous reduction of C=O group in that ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
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Abstract
The invention discloses a reduced vitamin K 2 The preparation method and the application thereof can be used for meeting the increasing demand of dental health. The preparation method comprises mixing oxidized vitamin K 2 Adding 7 times of purified water and 1 time of reducing agent according to the mass part, heating to 75-80 ℃, and carrying out reaction reduction for 1h; layering and reserving an upper layer; washing the upper layer with water at 70-80 ℃ to prepare the reduced vitamin K 2 (ii) a Adding cosolvent to obtain suspension; the application comprises preparing reduced vitamin K 2 Toothpaste, reduced vitamin K in said toothpaste 2 Accounting for 0.2 to 0.5 percent of the total weight of the toothpaste. The invention contains reduced vitamin K 2 The toothpaste contains vitamin K 2 And Chinese herbal medicine active ingredients, it has effects of brightening and whitening teeth, caring gingiva, and scientifically maintaining oral health.
Description
Technical Field
The invention belongs to the field of daily chemicals, and relates to reduced vitamin K 2 The preparation method and the application thereof can be used for meeting the increasing demand of dental health.
Background
In recent years, with the improvement of the living standard of people in China and the acceleration of the aging process, the needs for oral hygiene, gum maintenance and tooth health protection are increasing.
Vitamin K 2 Is a fat-soluble vitamin, is a group of compounds containing 2-methyl-1, 4 naphthoquinone mother nucleus, and is divided into vitamin K according to different side chain structures 1 Vitamin K 2 Vitamin K 3 Three major categories. Wherein vitamin K 1 And vitamin K 3 Is a single compound, and vitamin K 2 Different vitamin K is formed according to different isoprene contained in the side chain 2 The number of n containing isoprene which has clinical value at present is different and is expressed by MK-n, namely MK-4, MK-7 and MK-9, and the standard of MK-7, MK-4 and MK-9 in the United states and China also have a large number of reports on good biological activity.
Clinically, vitamin K deficiency is associated with an increase in prothrombin time due to decreased prothrombin activity, and bleeding are typical symptoms of vitamin K deficiency. To date, dietary vitamin K recommended intakes have been determined based on the normal synthetic clotting factors of the liver, rather than the amount required for function in bone and vascular metabolism, and evidence accumulated in vitamin K recommended intakes established in the united states and united kingdom suggests that higher vitamin K intakes are required in other tissues, particularly bone and arteries, to meet the carboxylation required for the local production of Gla-protein. Population studies suggest that circulating vitamin K, uncarboxylated osteocalcin (ucOC) and carboxylated osteocalcin (ccoc) are closely related, the ratio of the uncarboxylated osteocalcin to the carboxylated osteocalcin is the most sensitive sign of the nutritional status of bone vitamin K, the dietary intake of vitamin K is insufficient to ensure carboxylation of all osteocalcin, and about 10-30% of osteocalcin in healthy people is in low carboxylation state, thereby inducing diseases such as hemorrhage, bone health (osteoporosis), cardiovascular disease and the like.
Studies have shown that MK-1 and MK-3 are converted in vivo by intestinal bacteria into vitamin K 2 It has biological activity.
Vitamin K 2 The biological activity of the vitamin K is that in the biological oxidation metabolism process, lipophilic oxidized quinoid structure obtains hydrogen proton transferred upstream and vitamin K reduced by electron 2 Reduction to hydrophilic vitamin K 2 Thereby providing the ability of metabolism to transfer electrons and protons and exerting vitamin K 2 Physiological effects in human metabolism. The invention prepares the hydrophilic reduced vitamin K with physiological activity in vitro 2 Specific oxidation type vitamin K 2 Has better bioavailability and efficacy.
Disclosure of Invention
The invention aims to provide reduced vitamin K 2 A process for the preparation thereof and the use thereof.
One purpose of the vitamin K is to provide a reduced form of vitamin K 2 The preparation method comprises mixing lipophilic oxidized vitamin K 2 Reducing to obtain hydrophilic reduced vitamin K 2 The method comprises the following steps:
step 1, oxidizing vitamin K 2 Adding 7 times of purified water and 1 time of sodium borohydride, potassium borohydride and anhydrous sodium nitrite according to the mass partsAny one of sodium sulfate, lithium aluminum hydride, ferrous sulfate and sodium dithionite is used as reducing agent, and lipophilic oxidized vitamin K is added 2 The quinoid structure of (A) is oxidized into reduced vitamin K 2 The alcohol structure of (1); heating to 75-80 ℃, and reducing for 1h;
the reducing agent is preferably sodium dithionite.
Step 2, layering, removing a lower water layer and keeping an upper layer;
step 3, washing the upper layer with hot water at the temperature of 70-80 ℃ for 3-4 times;
step 4, vacuum drying to remove moisture to prepare the reduced vitamin K 2 ；
And 5, adding any one of 1 time of propylene glycol, tween 80, polyethylene glycol 400 and polyethylene glycol 600 as a cosolvent, stirring to prepare a suspension, sealing, and preserving heat at 40 ℃ for storage for later use.
The cosolvent is preferably polyethylene glycol 400.
The oxidized form of vitamin K 2 Comprises vitamin K 2 (MK-4) vitamin K 2 (MK-7) and vitamin K 2 (MK-9).
The oxidized form of vitamin K 2 Preferably vitamin K 2 (MK-7)。
The oxidized form of vitamin K 2 (MK-4) and oxidized vitamin K 2 (MK-7) and oxidized vitamin K 2 (MK-9) the structural formula, molecular formula and molecular weight are respectively as follows:
the obtained reduced vitamin K 2 Comprising reduced vitamin K 2 (MK-4) reduced vitamin K 2 (MK-7) and reduced vitamin K 2 (MK-9).
The reduced vitamin K 2 Preferably reduced vitamin K 2 (MK-7)。
The reduced vitamin K 2 (MK-4) reduced formVitamin K 2 (MK-7) and reduced vitamin K 2 (MK-9) the structural formula, molecular formula and molecular weight are respectively as follows:
the second purpose of the invention is to provide a method for preparing reduced vitamin K 2 Toothpaste, said reduced vitamin K 2 Refers to the reduced vitamin K prepared 2 Suspension of reduced vitamin K after elimination of the cosolvent 2 The actual value of the vitamin K in the toothpaste is 0.2-0.5 percent of the total mass of the toothpaste, namely the reduced vitamin K of the toothpaste 2 The content of the toothpaste is 0.2 to 0.5 percent of the total mass of the toothpaste.
Preferably, the reduced vitamin K 2 Is vitamin K 2 (MK-7)。
Preferably, the toothpaste also comprises the following components by mass: 0.5 to 1 percent of Chinese herbal medicine extract; 30 to 35 percent of a friction agent; 30 to 35 percent of wetting agent; 0.5 to 2.5 percent of adhesive; 0.5 to 2.5 percent of foaming agent; 0.05 to 0.25 percent of flavoring agent; 0.5 to 1 percent of essence; 20 to 40 percent of purified water.
Further, the Chinese herbal medicine extract is any one of water-soluble water-alcohol extract of dandelion, fibrauretine, cold water-soluble extract of houttuynia cordata and water-alcohol extract of panax notoginseng saponins.
Further, the traditional Chinese medicine extract is a water-alcohol extract of dandelion.
The third purpose of the invention is to provide a vitamin K containing reduced form 2 The preparation method of the toothpaste comprises the following steps:
step 1, in reduced form vitamin K 2 Adding herbal extracts, wetting agent and purified water to the suspension, and stirring at high speed and tangent in a paste machineStirring to obtain emulsion;
step 2, uniformly mixing the emulsion with a friction agent, an adhesive, a foaming agent and a flavoring agent through a premixing pot, slowly adding the uniformly mixed materials into a paste making machine, stirring at a high speed, grinding and degassing in vacuum;
step 3, adding essence, continuing stirring, grinding and vacuum degassing to obtain toothpaste;
step 4, filling, sealing, packaging and inspecting the paste body in a toothpaste filling production line to obtain the reduced vitamin K 2 A toothpaste.
Further, the obtained reduced vitamin K-containing extract is subjected to a treatment 2 Reduction type vitamin K of toothpaste 2 Content detection of (2), the reduced vitamin K 2 The content range should be 90% to 110% of the indicated value.
Further, the abrasives used in the formulation are: calcium carbonate, calcium hydrogen phosphate, calcium pyrophosphate, silica, aluminum hydroxide, hydrated silicic acid 1-2, preferably silica, calcium carbonate, more preferably silica.
Further, the amount of the rubbing agent is 30% to 35%, preferably 30%, 32%, 35%, more preferably 30% (when two are used, in a preferable ratio = 1.
Further, the wetting agents used in the formulation were: sorbitol, xylitol, glycerol and propylene glycol, preferably sorbitol, xylitol and glycerol, more preferably xylitol and glycerol.
Further, the wetting agent is used in an amount of 30% to 35%, preferably 30%, 32%, 35%, more preferably 30% (when two are used, in a preferred ratio = 1.
Further, the binders used in the formulation were: CMC (sodium carboxymethyl cellulose), xanthan gum, sodium alginate, guar gum and carrageenan, preferably sodium carboxymethyl cellulose and xanthan gum, more preferably sodium carboxymethyl cellulose.
Further, the binder is used in an amount of 0.5% to 2.5%, preferably 0.5%, 1.0%, 2.0%, more preferably 0.5% (when two are used, in a preferred ratio = 1.
Further, the blowing agents used in the formulation were: one of sodium lauryl sulfate, sodium N-lauroyl sarcosinate, sodium methylcocoacanthyl taurate and sodium phenolglutamate, preferably sodium lauryl sulfate and sodium N-lauroyl sarcosinate, more preferably sodium lauryl sulfate.
Further, the amount of the foaming agent is 0.5% to 2.5%, preferably 0.5%, 1.0%, 2.0%, more preferably 0.5%.
Further, the flavoring agents used in the formulation are: one of sucrose, saccharin, sodium cyclamate and sodium biuret, preferably sucrose, saccharin and sodium cyclamate, and more preferably saccharin.
Further, the amount of the flavoring agent is 0.05% to 0.25%, preferably 0.05%, 0.10%, 0.20%, more preferably 0.10%.
Further, the essence used in the formula is: one of oleum Menthae Dementholatum, lemon oil, spearmint oil, orange oil, mandarin oil, oleum Caryophylli, oleum Cinnamomi, oleum Foeniculi and Borneolum Syntheticum, preferably oleum Menthae Dementholatum, lemon oil and spearmint oil, more preferably spearmint oil.
Further, the amount of the essence is 0.5% -1.0%, preferably 0.5%, 0.6%, 0.8%, more preferably 0.5%.
Containing reduced vitamin K 2 Toothpaste product quality stability considerations included:
(1) Containing reduced vitamin K 2 The toothpaste is mainly studied to contain the reduced vitamin K 2 Stability in toothpaste, investigation by influencing reduced vitamin K 2 Humidity and temperature factors, 6 months accelerated testing was performed.
(2) Focus on investigating appearance character and reducing vitamin K in toothpaste 2 The content was varied.
(3) Examination conditions were as follows: high temperature (60 ℃,40 ℃), high humidity (25 ℃ RH 92.5%), accelerated test (time points 0 month, 3 months, 6 months).
(4) Investigation results of reduced form-containing vitamin K 2 The toothpaste has no obvious change of appearance character, reduced vitamin K 2 The content is in the index control range, and the content of the reduced vitamin K is examined 2 The toothpaste product has stable quality.
The beneficial effects of the invention include:
vitamin K 2 Is an active ingredient of vitamin K, and the prior art researches show that the vitamin K 1 And vitamin K 3 Only converted into vitamin K 2 Only work, under physiological conditions, vitamin K 2 Conversion to reduced vitamin K 2 The physiological function of transferring electrons and protons is achieved. Vitamin K is caused by nutritional and dietary deficiency, and intestinal metabolism disorder 2 Deficiency of (A) leading to vitamin K dependence 2 The activity of low carboxylation of the carboxylated glutamic acid residue protein and the production of inactive Gla protein to bind calcium is reduced, coagulation disorder is initiated, bleeding is caused, and inflammation is caused. Vitamin K 2 In addition to the effects of the traditional clotting mechanism, gla-containing proteins have a variety of regulatory functions, including clotting, bone turnover, vascular repair, regulation of cell circulation, intercellular adhesion, and signaling. The toothpaste formula of the invention contains reduced vitamin K 2 And/or active ingredients of Chinese herbal medicines, and has the effects of brightening and whitening teeth, caring gingiva, scientifically maintaining oral health and the like.
Detailed Description
The present invention will be described in detail with reference to specific examples.
Example 1: reduced form vitamin K 2 Preparation of (MK-4)
Weighing oxidized vitamin K with the content of 97 percent 2 (MK-4) 150g of the crude product is put into a 2000mL three-necked flask with a stirrer, 1050g of purified water is added, 150g of sodium hydrosulfite is added, the temperature is raised to 75 to 80 ℃ for reaction for 1 hour, after the reaction is finished, the mixture is kept stand for layering, the lower water layer is removed, the upper layer is washed 4 times by 2000mL of hot water with the temperature of 70 to 80 ℃, and washed reduced vitamin K is collected 2 Detecting the supernatant with HPLC, and detecting the oxidized vitamin K 2 (MK-4) 0% reduced vitamin K 2 The content of (MK-4) is 100%. Adding 150g polyethylene glycol 400 for dissolving to obtain suspension, sealing, and storing at 40 deg.C.
Example 2: reduced form vitamin K 2 Preparation of (MK-7)
Weighing oxidized vitamin K with the content of 96 percent 2 (MK-7) 150g is put into a 2000mL three-neck flask with stirring, 1050g of purified water is added, 150g of sodium hydrosulfite is added, the temperature is increased to 75-80 ℃, the reaction is carried out for 1 hour, the mixture is kept stand and layered after the reaction is finished, the lower water layer is removed, the upper layer is washed for 4 times by 2000mL hot water with the temperature of 70-80 ℃, and the washed reduced vitamin K is collected 2 Detecting the supernatant with HPLC, and detecting the oxidized vitamin K 2 (MK-7) 2% reduced vitamin K 2 The (MK-7) content was 98%. Adding 150g polyethylene glycol 400 for dissolving to obtain suspension, sealing, and storing at 40 deg.C.
Example 3: reduced form vitamin K 2 Preparation of (MK-9)
Weighing oxidized vitamin K with the content of 97 percent 2 (MK-9) 100g is put into a 2000mL three-neck flask with stirring, 700g of purified water is added, 100g of sodium hydrosulfite is added, the temperature is increased to 75-80 ℃, the reaction is carried out for 1 hour, the mixture is kept stand and layered after the reaction is finished, the lower water layer is removed, the upper layer is washed for 4 times by 2000mL hot water with the temperature of 70-80 ℃, and the washed reduced vitamin K is collected 2 Detecting the supernatant with HPLC, and detecting the oxidized vitamin K 2 (MK-9) 3% reduced vitamin K 2 The content of (MK-9) was 97%. Adding 100g polyethylene glycol 400 for dissolving to obtain suspension, sealing, and storing at 40 deg.C.
Example 4: containing reduced vitamin K 2 (MK-4) toothpaste formula
100 pieces of the formula are prepared in batches, and the specification is 120 g/piece.
Containing reduced vitamin K 2 (MK-4) prescription Table
Example 5: containing reduced vitamin K 2 (MK-7) toothpaste formula
100 pieces of the formula are prepared in batches, and the specification is 100 g/piece.
Containing reduced vitamin K 2 (MK-7) prescription Table
Example 6: containing reduced vitamin K 2 (MK-9) toothpaste formula
100 pieces of the formula are prepared in batches, and the specification is 60 g/piece.
Containing reduced vitamin K 2 (MK-9) prescription Table
Example 7: containing reduced vitamin K 2 (MK-4) toothpaste preparation
Reduced vitamin K prepared in example 1 2 (MK-4) suspension, deducting cosolvent, weighing 60g reduced vitamin K 2 (MK-4), adding 60g of the water-alcohol extract of dandelion, 1800g of wetting agent xylitol, 1800g of glycerol and 4428g of purified water in sequence, and stirring in a paste making machine with high-speed tangential stirring to prepare emulsion; slowly adding 3600g of abrasive silicon dioxide uniformly mixed by a premixing pot, 60g of binder carboxymethylcellulose sodium, 60g of foaming agent sodium dodecyl sulfate and 12g of corrigent saccharin, stirring at a high speed, grinding and degassing in vacuum, adding 60g of essence spearmint oil, continuously stirring, grinding and degassing in vacuum to prepare toothpaste, and finally filling, sealing a tube, packaging and inspecting the toothpaste, wherein each 120g is prepared into about 100 strips.
Example 8: containing reduced vitamin K 2 (MK-7) toothpaste preparation
Reduced vitamin K prepared in example 2 2 (MK-7) suspension, deducting cosolvent, weighing 50g reduced vitamin K 2 (MK-7) adding 50g of cold water-soluble extract of houttuynia cordata, 1500g of xylitol as a wetting agent, 1500g of glycerol and 3690g of purified water in sequence, and stirring in a paste making machine with high-speed tangential stirring to obtain an emulsion; then adding 3000g of abrasive silicon dioxide, 50g of binder sodium carboxymethyl cellulose, 50g of foaming agent sodium dodecyl sulfate and 10g of corrigent saccharin, stirring at high speed, grinding, vacuum degassing, and adding essenceSpearmint oil 50g, continuously stirring, grinding, vacuum degassing to obtain toothpaste body, and finally filling, sealing, packaging and inspecting the toothpaste body to obtain about 100 strips of the toothpaste body each 100 g.
Example 9: containing reduced vitamin K 2 (MK-9) toothpaste preparation
Reduced vitamin K prepared in example 3 2 (MK-9) suspension, minus co-solvent, 30g reduced vitamin K was weighed 2 (MK-9) adding 30g of the hydroalcoholic extract of dandelion, 1800g of the wetting agent xylitol and 2214g of purified water in sequence, and stirring in a paste making machine with high-speed tangential stirring to prepare emulsion; slowly adding 900g of abrasive silicon dioxide, 900g of calcium carbonate, 30g of sodium carboxymethyl cellulose as binder, 30g of sodium lauryl sulfate as foaming agent and 6g of saccharin as flavoring agent, uniformly mixing in a premixing pot, stirring at a high speed, grinding, vacuum degassing, adding 30g of essence and spearmint oil, continuously stirring, grinding and vacuum degassing to obtain toothpaste, and finally filling, sealing a tube, packaging and inspecting the toothpaste to obtain about 100 toothpaste each 60 g.
Containing reduced vitamin K 2 Toothpaste product detection
(1) Containing reduced vitamin K 2 Examination of appearance of toothpaste products
The toothpaste prepared by the embodiment of the invention has the advantages of fine and smooth appearance, uniform paste, foreign matter existence, appearance and character check, and the check result is shown in table 1.
TABLE 1 reduced form-containing vitamin K 2 Appearance character inspection of toothpaste
| Examples of the invention | Appearance of the product | Traits | Determination |
| Example 1 | Uniform paste and no foreign matter | The surface of the paste appears white under natural light | Within the range specified by the standard |
| Example 2 | Uniform paste and no foreign matter | The surface of the paste appears white under natural light | Within the range specified by the standard |
| Example 3 | Uniform paste and no foreign matter | The surface of the paste appears white under natural light | Within the range specified by the standard |
According to the results of three batches of examples, the vitamin K respectively contains reduced vitamin K 2 (MK-4) reduced vitamin K 2 (MK-7) reduced vitamin K 2 (MK-9) the toothpaste prepared by the example has the appearance and the properties within the standard control range and meets the quality standard.
(2) Reduced form vitamin K 2 Product content detection
Reduced vitamin K in toothpaste prepared according to the invention 2 The contents were measured separately and the results are shown in Table 2.
TABLE 2 vitamin K 2 Test condition table
According to the result of the detection, containing a reduced formVitamin K 2 The toothpaste examples respectively use the oxidation type vitamin K with the content meeting the regulation 2 (MK-4) and oxidized vitamin K 2 (MK-7) oxidized vitamin K 2 (MK-9) preparation of reduced vitamin K 2 (MK-4) reduced vitamin K 2 (MK-7) reduced vitamin K 2 (MK-9) reduced vitamin K is shown by measuring the content of the ointment 2 The content of the oxidized vitamin K is slightly reduced compared with that before the feeding, and the oxidized vitamin K 2 Slightly increased, the increase and decrease amplitude of the product is within the index control range, and the product quality is stable. The reason for the increased oxidation is the oxidized form of vitamin K 2 Generally, it is relatively stable, and the reduced form is less stable than the oxidized form, and the oxidation to the stable oxidized form is relatively slow in the presence of air.
(3) Containing reduced vitamin K 2 Stability test of toothpaste
Containing reduced vitamin K 2 Toothpaste in view of reduced vitamin K 2 The stability of (A) is slightly poor, and the main index for stability inspection is reduced vitamin K 2 The content varied during storage. The examination method adopts a high-temperature, high-humidity and accelerated test method, and the examination results are shown in tables 3, 4 and 5.
TABLE 3 reduced vitamin K at high temperature conditions 2 Examination of content stability
TABLE 4 reduced vitamin K under high humidity conditions 2 Examination of content stability
TABLE 5 reduced vitamin K 2 Content acceleration test
Containing reduced vitamin K 2 The toothpaste is shown by a 6-month stability acceleration test that the property index of the toothpaste has no obvious change, and the property and quality of the toothpaste can be ensured; reduced vitamin K in functional component 2 The content is slightly changed, but is within the index control range. Oxidized form of vitamin K 2 Although there is an increase, the oxidized form of vitamin K 2 Also belongs to an active ingredient, and the physiological activity of the active ingredient is slightly lower than that of reduced vitamin K 2 . High temperature and high humidity in experiment shows that reduced vitamin K 2 Has good moisture resistance and heat resistance, and contains vitamin K 2 The quality is only structural interconversion and no qualitative change is generated. The stability research shows that the vitamin K contains reduced form 2 The toothpaste has no harsh storage condition, and can ensure the quality of the toothpaste when being stored and used at normal temperature.
(4) Reduced vitamin K of the present invention 2 Content detection method
1 reagent
1.1 n-hexane: pure chromatography
1.2 ethyl acetate: pure chromatography
1.3 n-hexane: analytical purity
2 reference substance
2.1 reduced vitamin K 2 Comparison products: the product is self-made by a company, and the purity is 99.8 percent
3 apparatus
3.1 high performance liquid chromatograph
3.2 electronic balance
4 chromatographic conditions
4.1 silica gel column (250 mm. Times.4.6 mm,5 μm)
4.2 detection wavelength: 270nm
4.3 column temperature: 25 deg.C
4.4 mobile phase: n-hexane: ethyl acetate =99.5:0.5 (V/V)
4.5 flow rate: 2mL/min
4.6 sample size: 20 μ L
5 preparation of control solutions
And (4) avoiding light. Precisely weighing reduced vitamin K 2 Control 1mg (to 0.01 mg) was placed in a 10mL brown flask and added3mL of n-hexane, carrying out ultrasonic oscillation for 5min to completely dissolve the n-hexane, adding the n-hexane to the scale, and shaking up. Precisely measuring 1mL of the solution, placing the solution in a 10mL brown volumetric flask, adding n-hexane to the scale, and shaking up to obtain a reference solution.
6 preparation of sample solution
And (4) avoiding light. Accurately weighing 2g (accurate to 0.001 g) of the content of the product, placing the product in a centrifuge tube, adding 2mL of n-hexane, carrying out ultrasonic oscillation for 10min, then centrifuging the product at the rotating speed of 4000 r/r for 3min, transferring the supernatant into a 100mL brown volumetric flask, and repeating the operation until the transfer is complete. And (3) fixing the volume of the normal hexane to a scale, shaking up, and filtering by using an organic microporous filter membrane of 0.45 mu m to obtain a sample solution.
7 measurement of
The control solution and the sample solution were taken at 20. Mu.L each, measured under the above conditions, and the liquid chromatography was recorded.
8 calculation of results
1) Reduced vitamin K in samples 2 Content w 1 (mg/g) as calculated by the following formula (1):
in the formula:
A 1 reduced vitamin K in sample solution 2 Peak area value of (a);
A 2 reduced vitamin K in control solutions 2 Peak area value of (a);
m 1 -sample mass in grams (g);
m 2 reduced vitamin K in control solutions 2 Mass in milligrams (mg);
v 1 the volume of the reference solution is determined by volume in mL;
v 2 the volume of the sample solution is determined by volume in mL;
f, the dilution times of the reference substance solution;
w 2 -reduced vitamin K 2 Quality of controlAnd (4) parts.
Claims (3)
1. Reduced vitamin K 2 Is characterized in that lipophilic oxidized vitamin K is added 2 Reducing to obtain hydrophilic reduced vitamin K 2 The method comprises the following steps:
step 1, oxidizing vitamin K 2 Adding 7 times of purified water and 1 time of reducing agent according to the mass part, heating to 75-80 ℃, and carrying out reaction reduction for 1h;
step 2, layering, removing a lower water layer and keeping an upper layer;
step 3, washing the upper layer with hot water at the temperature of 70-80 ℃ for 3-4 times;
step 4, vacuum drying to remove moisture to prepare the reduced vitamin K 2 ；
Step 5, adding 1 time of cosolvent, stirring to prepare a suspension, sealing, and storing at 40 ℃ for later use;
the cosolvent is any one of propylene glycol, tween 80, polyethylene glycol 400 and polyethylene glycol 600;
the reducing agent is any one of sodium borohydride, potassium borohydride, anhydrous sodium sulfite, lithium aluminum hydride, ferrous sulfate and sodium hydrosulfite.
2. Reduced vitamin K according to claim 1 2 The preparation method is characterized by comprising the following steps:
the oxidized form of vitamin K 2 Comprises oxidized vitamin K 2 MK-4 and oxidized vitamin K 2 MK-7 and oxidized vitamin K 2 Any one of MK-9;
the oxidized form of vitamin K 2 MK-4 and oxidized vitamin K 2 MK-7 and oxidized vitamin K 2 MK-9 has the following structural formula, molecular formula and molecular weight:
oxidation by oxygenType MK-4C 31 H 40 O 2 445.00
Oxidized MK-7C 46 H 64 O 2 649.00
Oxidized MK-9C 56 H 80 O 2 785.00。
3. Reduced vitamin K according to claim 1 2 The preparation method is characterized by comprising the following steps:
the obtained reduced vitamin K 2 Comprising reduced vitamin K 2 MK-4, reduced vitamin K 2 MK-7 and reduced vitamin K 2 Any one of MK-9;
the reduced vitamin K 2 MK-4, reduced vitamin K 2 MK-7 and reduced vitamin K 2 MK-9 has the following structural formula, molecular formula and molecular weight:
reduced MK-4C 31 H 42 O 2 447.00
Reduced MK-7C 46 H66O2 651.00
Reduced MK-9C56H82O 2 787.00。
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| CN107428645A (en) * | 2015-03-20 | 2017-12-01 | 诺西斯有限公司 | The reduction menadione of solid form |
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| US20190076343A1 (en) * | 2017-09-14 | 2019-03-14 | Gerald P. Curatola | Oral care formulations and methods for use |
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| JPS63179823A (en) * | 1987-01-19 | 1988-07-23 | Sunstar Inc | Composition for oral cavity |
| CN1553800A (en) * | 2001-07-16 | 2004-12-08 | ����˹���ѧ���»� | Napthoquinone derivatives as inhibitors of tau aggregation for the treatment of alzheimer's and related neurodegenerative disorders |
| EP2060256A1 (en) * | 2007-11-16 | 2009-05-20 | Gnosis S.p.A. | Pharmaceutical and nutraceutical compositions based on menaquinols |
| CN107428645A (en) * | 2015-03-20 | 2017-12-01 | 诺西斯有限公司 | The reduction menadione of solid form |
| CN104892370A (en) * | 2015-04-01 | 2015-09-09 | 浙江新和成股份有限公司 | Preparation method for reductive coenzyme Q10 |
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