• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    An NADH compound, and a formulation and application thereof, relating to the technical field of biomedicine and health care products. The NADH compound comprises NADH or its physiologically acceptable salt and L-carnitine or its physiologically acceptable salt, and can be used as a weight loss product.
    公开号:ES2786774A2
    申请号:ES201990087
    申请日:2017-12-22
    公开日:2020-10-13
    发明作者:Rongzhao Fu；Xieguo Yan；Zhu Dai
    申请人:Bontac Bio Eng Shenzhen Co Ltd；
    IPC主号:
    专利说明:

    [0002] Composition for coenzyme compound NADH, preparation and application thereof
    [0004] CROSS REFERENCE TO RELATED REQUESTS
    [0005] This application is the national phase of International Application No. PCT / CN2017118093 filed on December 22, 2017, the full content of which is incorporated herein by reference.
    [0006] TECHNOLOGY FIELD
    [0007] The invention relates to the field of biomedicine and health care products, in particular, to new formulations and new uses of coenzyme NADH in the field of medicine and health care.
    [0008] BACKGROUND
    [0009] Coenzyme NADH is a shortened form of nicotinamide adenine reduced dinucleotide. Nicotinamide adenine dinucleotide is a physiological substance present in all living cells, including human cells, and it has no side effects in the body. This substance is a cofactor for many enzymes that catalyze oxidation-reduction reactions and is called coenzyme I.
    [0010] The coenzyme NADH is generated in the cycle of citric acid glycolysis and respiration in living organisms, acting as a hydrogen donor in the enzymatic reaction. It is involved in many physiological activities, such as the metabolism of cellular material, energy synthesis, and cellular DNA repair, and is a control marker in the energy production chain of the mitochondria. The most important role of coenzyme NADH is to act as the driving force for cellular respiration. The ATP produced by direct metabolism through glucose metabolism is very small. However, the metabolically produced coenzyme NADH can produce a large amount of ATP through an oxidative reaction by transferring electrons from phosphoric acid, thus meeting the energy needs of the body.
    [0011] Coenzyme NADH is widely used in catalytic chemical reactions, API production, health care products, and cosmetics. Reports on the application of coenzyme NADH in the field of medicine and health care products have been widely reported, for example, to combat aging, prevention and chronic disease treatment, but there have been no reports on using coenzyme NADH for weight loss.
    [0012] According to WHO statistics, more than 1.4 billion adults over the age of 20 are overweight; Among overweight adults, more than 200 million men and nearly 300 million women are obese. All in all, more than 10% of adults globally are obese. Additionally, 44% of the burden of diabetes, 23% of the burden of ischemic heart disease, and 7% to 41% of the burden of certain cancers can be attributed to overweight and obesity. According to statistics, at least 2.8 million adults die each year from being overweight or obese. Being overweight and obese are now the fifth highest risk of death worldwide.
    [0013] In 2016, the famous British medical journal "Lancet" published a report on the world adult weight survey, which shows that the obese population of adults worldwide has surpassed the slimmer population, and China has overtaken the United States to become the country with the largest obese population in the world. Among which, the number of obese men in China is 43.2 million, and the number of obese women is 46.4 million. The absolute number of obese people in China has reached the highest in the world.
    [0014] For overweight and obesity, although a large number of research and development forces have been invested at home and abroad, there are only a handful of drugs that target weight loss approved by the Food and Drug Administration. due to the difficulty in research and development. But these drugs still have the following two problems: 1. The administration of the drug is associated with weight-related diseases, such as hypertension, type 2 diabetes, or hyperlipidemia; 2. Long-term use of these drugs can cause different levels of side effects such as headache, dizziness, fatigue, nausea, and dry mouth, and there will be a relapse after stopping the drug.
    [0015] With the popularization of the green healthy living concept, more and more people are craving for natural slimming products, especially those with L-carnitine. L-carnitine is popular with people because it is derived from red meat such as beef and pork, and it has no toxic side effects on the human body.
    [0016] L-carnitine, also called vitamin BT or carnitine by translation through pronunciation. Its chemical name is p-hydroxy-Y-trimethylammonium butyrate, which is an amino acid that promotes the conversion of fat into energy. As a weight loss product, Lcarnitine is mainly characterized by (1) only reducing fat without reducing moisture, (2) doubling the effect of exercise on weight loss, and (3) being the safest and healthiest weight loss supplement. At present, L-carnitine has been applied in the fields of medicine, health care products and food, and has been prescribed as a multipurpose nutrient by Switzerland, France, the United States and the World Organization of health. The GB2960-1999 Standards for Food Additive Uses in China stipulate that L-carnitine tartrate is a food nutrition enhancer, which can be applied to chewable tablets, soft drinks, capsules, powdered milk and milk drinks.
    [0017] The role of L-carnitine in fat metabolism has been confirmed to play the role of "fat transporter". Specifically, the place where fat is oxidized and broken down is in the mitochondria. If fat does not enter the mitochondria, no matter what exercise or diet is like, it cannot be consumed. To enter the mitochondria, fat must first cross the mitochondrial membrane, and crossing this barrier must depend on the transport function of the L-carnitine carrier. If fat is compared to coal, and mitochondria are compared to a kettle, L-carnitine is equivalent to a shovel, which feeds coal (fat) into the kettle (mitochondria) for combustion.
    [0018] People routinely take less than 50 mg of L-carnitine from their diet every day. However, to achieve the desired state of health, ordinary adults should consume no less than 500 mg of L-carnitine per day. Obese people and vegetarians, especially women, need more. Therefore, L-carnitine must be supplemented in addition to food to meet the requirements for maintaining an ideal body. However, the study has found that although people take L-carnitine to lose weight up to 1 ~ 3g, there is no obvious increase in L-carnitine content in muscle, which cannot maximize the effect of the product, which results in an absolute bioavailability of L-carnitine being only 15.9 ± 4.9% and therefore reduced effect on the weight loss effect.
    [0019] SUMMARY
    [0020] For the technical problem of low bioavailability and reduced effect on weight loss for the L-carnitine weight loss products currently on the market mentioned in the above background, the purpose of the present invention is to develop a new use of coenzyme NADH in weight loss, in order to obtain a new weight loss product, in order to solve the aforementioned deficiencies of L-carnitine weight loss products.
    [0021] To achieve the above goal, the inventor has carried out an extensive and long-term experimental study. The metabolic process of fat includes the following two stages: the first stage: fatty acids are transported from the outside of the mitochondria to the inside of the mitochondria by L-carnitine; The second stage: fatty acids undergo beta-oxidative breakdown in mitochondria to produce energy. The inventor discovered that the second stage of fat metabolism requires the participation of the coenzyme NADH, which hinders the metabolism of fats when the coenzyme NADH is deficient in the body. Taking L-carnitine and enhancing exercise can actually introduce more fatty acids into the mitochondria for oxidation, and the human body can also self-regulate to produce more coenzyme NADH to speed up oxidation. However, the above is not enough to lose enough fat, because the synthesis of coenzyme NADH in the body will not increase much in a short time. In this way, the fatty acids transported to the mitochondria cannot be consumed in a timely manner, thus inhibiting the fatty acid from being transported back to the mitochondria; then the human body will self-regulate and metabolize excess L-carnitine. This is why a lot of L-carnitine is taken in, but no significant increase in L-carnitine is found in muscle.
    [0022] Based on the foregoing study by the inventor, the present invention provides a composition for coenzyme NADH compound comprising the following components in parts by weight: coenzyme NADH or a physiologically acceptable salt thereof; and an L-carnitine or a physiologically acceptable salt thereof. The physiologically acceptable salt of coenzyme NADH and L-carnitine includes all known physiologically acceptable acid and base salt-forming substances, of which a sodium salt of coenzyme NADH and an L-carnitine tartrate are more preferred.
    [0023] Preferably, the composition comprises the following components in parts by weight: 1 to 10% coenzyme NADH or a physiologically acceptable salt thereof, 1 to 10% L-carnitine or a physiologically acceptable salt thereof, 5 ~ 50% of an oil phase, 20 ~ 70% of an emulsifier and 0 ~ 50% of a co-emulsifier.
    [0024] Preferably, the oil phase is selected from at least one of soybean oil, ethyl oleate, isopropyl myristate, isopropyl palmitate, corn oil, castor oil, Caprylic / Capric Triglyceride, Glycerol Monooleate, Oleic Acid, Olive Oil, Sesame Oil, Peanut Oil, and Almond Oil.
    [0025] Preferably the emulsifier is a non-ionic surfactant.
    [0026] More preferably, the emulsifier is selected from at least one of polyoxyethylene castor oil, hydrogenated polyoxyethylene castor oil, polyethylene glycol-15 stearate, oleic acid, polyethylene glycol, glyceride, phenyl octyl polyethylene glycol ether, octanoic acid, capryl caproyl macrogolgol 188 , polysorbate 80, liquid lecithin, sucrose laurate, sucrose palmitate, sucrose stearate, polyethylene glycol, glyceride and glycerol, polyethylene glycol-75 stearate.
    [0027] Preferably, the co-emulsifier is selected from at least one of ethanol, propylene glycol, polyethylene glycol 200, polyethylene glycol 400, and isopropanol, 1,2-propanediol, n-butanol, diethylene glycol, monoethyl ether, and propylene carbonate.
    [0028] Preferably, the above NADH coenzyme compound composition is prepared by means of a preparation method comprising the steps of: weighing a prescribed amount of an oil phase, an emulsifier, and a co-emulsifier into a vial, and adding an amount prescribed coenzyme NADH or a physiologically acceptable salt thereof to mix them uniformly to obtain a clear liquid; further add a prescribed amount of L-carnitine or a physiologically acceptable salt thereof to fully stir at 37 ° C for 1 hour to completely dissolve, thus obtaining the product. The NADH coenzyme compound composition can be filled directly into a soft capsule for oral administration, or it can be dispersed in a pharmaceutical excipient as a carrier material, compressed into a tablet for use, or added to a sustained release material to prepare a preparation. launch.
    [0029] The present invention further provides an oral preparation of coenzyme compound NADH comprising the composition for coenzyme compound NADH provided above by the present invention, and the oral preparation is preferably a tablet preparation or a capsule preparation.
    [0030] Preferably, in addition to the above NADH coenzyme compound composition, the oral preparation further comprises a pharmaceutical excipient, and the pharmaceutical excipient comprises the following components in parts by weight: 10 ~ 70% of an adsorbent, 10 ~ 80% of a diluent 0 ~ 10% of an adhesive, 5 ~ 10% of a disintegrator, 0 ~ 3% of a flavoring agent, and 0.5 ~ 4% of a lubricant; a weight ratio of the pharmaceutical excipient to composition for coenzyme compound NADH is 20: 1 ~ 5: 2.
    [0031] Preferably, the adsorbent is selected from at least one of anhydrous calcium chloride, calcium phosphate, calcium carbonate, magnesium carbonate, magnesium oxide, microsilica, microcrystalline cellulose, lactose, aluminum hydroxide gel powder, chloride sodium, pregelatinized starch, powdered sucrose, powdered glucose, mannitol, sorbitol starch, cyclodextrin, sodium carbonate, sodium bicarbonate, calcium sulfate, povidone, polyethylene glycol 4000 and polyethylene glycol 6000.
    [0032] Preferably, the diluent is selected from at least one of microcrystalline cellulose, calcium hydrogen phosphate, lactose, starch, dextrin, mannitol, powdered glucose, sucrose powder, and sorbitol.
    [0033] Preferably, the adhesive is selected from at least one of polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, various concentrations of ethanol solution, and water.
    [0034] Preferably, the disintegrator is selected from at least one of cross-linked sodium carboxymethyl cellulose, cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, low substituted hydroxypropyl cellulose, and partially pregelatinized starch.
    [0035] Preferably, the flavoring agent is selected from at least one of stevioside, aspartame, citric acid, food flavor, lactose, glucose, sucrose, and mannitol.
    [0036] Preferably, the lubricant is selected from at least one of micronized silica gel, magnesium stearate, talc, and sodium stearyl fumarate.
    [0037] Preferably, the oral preparation of the above coenzyme compound NADH can be prepared by the method according to any of the following 1 to 3:
    [0038] 1. Weigh the above NADH coenzyme compound composition and various pharmaceutical excipients according to the ratio, add a soft material made of a diluent, binder, flavoring agent and partial disintegration agent after the composition for compound of coenzyme NADH is adsorbed by the adsorbent to sieve the granules with 18 mesh or 20 mesh screen and dry to obtain dry granules; then sieve the dry granules with 18 mesh or 20 mesh sieve, add a lubricant and the remaining disintegrant to mix and compress uniformly, to obtain a preparation of oral tablet of coenzyme compound NADH;
    [0039] 2. Weigh the above composition for coenzyme compound NADH and various pharmaceutical excipients according to the ratio, mix evenly with the other pharmaceutical excipients after the composition for coenzyme compound NADH it is adsorbed by the adsorbent, and compressed directly to obtain an oral tablet preparation of coenzyme compound NADH;
    [0040] 3.
    [0041] The present invention further provides a new use of coenzyme NADH in the field of medicine and health products, that is, a use of the above coenzyme NADH composition containing coenzyme NADH as a main component or oral preparation of coenzyme compound NADH above in the preparation of a slimming product.
    [0042] The present invention further provides a method of weight loss, specifically, comprising the steps of administering a physiologically acceptable amount of the above coenzyme compound NADH composition or a physiologically acceptable amount of the oral preparation of the above coenzyme NADH compound for weight loss.
    [0043] Beneficial effects:
    [0044] Compared to the prior art, the present invention has the following advantages:
    [0045] 1. The present invention combines coenzyme NADH with L-carnitine for the first time to provide a new slimming product, which compensates for the lack of bioavailability of L-carnitine due to the lack of coenzyme NADH during the simple addition of L- carnitine in the process of fat metabolism, and has a greater effect on weight loss compared to existing L-carnitine-only weight loss products.
    [0046] 2. The composition for coenzyme compound NADH of the active ingredient, oil phase, emulsifier and co-emulsifier provided by the present invention can be spontaneously emulsified in the body to form small emulsion droplets with a particle size ranging from 10 to 100 nm after oral administration, which greatly increases the area of contact of the drug with the medium and the mucosa, promotes oral absorption of the drug, further increases the effect on weight loss and improves the bioavailability of L-carnitine.
    [0047] 3. The composition for coenzyme NADH compound provided by the present invention is a thermodynamically stable uniform system, which significantly improves the stability of coenzyme NADH and L-carnitine, and can achieve long-term drug delivery of the product.
    [0048] 4. The preparation process for the composition for coenzyme NADH compound and the preparation thereof provided by the present invention is simple and easy without special instruments or equipment, having advantages of low cost, energy saving and environmental protection.
    [0049] BRIEF DESCRIPTION OF THE DRAWINGS
    [0050] Figure 1 is an in vitro cumulative release profile of an oral tablet preparation of the coenzyme NADH compound provided by the present invention, where the abscissa is the release time (h) and the ordinate is the cumulative release percentage ( %);
    [0051] Figure 2 is an electron micrograph of an oral tablet preparation of the coenzyme compound NADH provided by the present invention.
    [0052] DESCRIPTION OF THE REALIZATIONS
    [0053] The present invention will be further described in detail below with reference to the specific embodiments and the accompanying drawings. The following examples are illustrative of the invention, and the present invention is not limited to the following examples.
    [0054] The raw materials and chemical reagents used in the following embodiments are all commercially available.
    [0055] Embodiment 1
    [0056] 1. The formula of the oral tablet preparation of the coenzyme compound NADH is as follows:
    [0057] Coenzyme NADH 5 g
    [0058] L-carnitine 5 g
    [0059] Soybean oil 22 g
    [0061] Polyoxyethylene castor oil 40 g
    [0063] Lactose 25 g
    [0064] Microcrystalline cellulose PH101 100 g
    [0066] Calcium hydrogen phosphate 80 g
    [0067] Hydroxypropylmethylcellulose 12 g
    [0068] Low substituted hydroxypropyl cellulose 30 g
    [0070] Stevioside 3 g
    [0072] Sodium stearyl fumarate 10 g
    [0074] Total 1000 tablets / granules 2. The preparation method is as follows:
    [0075] Each component is weighed according to the above formula, and soybean oil, polyoxyethylene castor oil, and coenzyme NADH are added into a vial to mix evenly to obtain a clear liquid; then the L-carnitine is added to stir completely at 37 ° C for 1 hour to completely dissolve, thus obtaining a composition solution for coenzyme compound NADH.
    [0076] Next, the solution of the composition for coenzyme compound NADH is adsorbed with lactose, and after the adsorption is complete, microcrystalline cellulose PH101, calcium hydrogen phosphate, stevioside, hydroxypropylmethylcellulose and 3/4 of the amount of low substituted hydroxypropyl cellulose to mix evenly and sieve on 20 mesh to prepare granules, then dry to sieve again on 18 mesh to prepare whole granules. The obtained granules can be filled into an acid resistant capsule DRcaps to obtain an oral capsule preparation of coenzyme compound NADH; or the sodium stearyl fumarate and the remaining low substituted hydroxypropyl cellulose are added to mix uniformly and compress to obtain the oral tablet preparation of the coenzyme compound NADH.
    [0077] 3. Determination for decay
    [0078] 6 pieces of the prepared oral tablet preparation of the coenzyme compound NADH are taken into a 250 ml beaker, and gently shaken by adding 100 ml of water at 20 ± 1 ° C, to record a time through screen No. 2, which is 68 ± 2s. The suspension obtained is filtered through a 0.45 µm microporous membrane to remove the insoluble solid adjuvant, and the particle size is determined to be 32 ± 3 nm.
    [0079] Embodiment 2
    [0080] 1. The formula of the oral tablet preparation of the coenzyme compound NADH is as follows:
    [0081] Coenzyme NADH 8 g
    [0082] L-carnitine 4 g
    [0083] Ethyl oleate 20 g
    [0084] Polyoxyethylene castor oil
    [0085] 35 g
    [0086] hydrogenated
    [0087] Diethylene glycol, monoethyl ether 15 g
    [0088] Anhydrous calcium chloride 20 g
    [0089] Microcrystalline cellulose PH101 120 g
    [0090] Polyvinylpyrrolidone 5 g
    [0091] Sodium croscone 25 g
    [0092] Aspartame 3 g
    [0093] Microsilica gel 10 g
    [0094] Magnesium stearate 2 g
    [0095] Total 1000 tablets / granules
    [0096] 2. The preparation method is as follows:
    [0097] Each component is weighed according to the above formula, and the ethyl oleate, the hydrogenated polyoxyethylene castor oil, diethylene glycol, monoethyl ether and the coenzyme NADH are added into a vial to mix them evenly to obtain a clear liquid; then the L-carnitine is added to stir completely at 37 ° C for 1 hour to completely dissolve, thus obtaining a solution of the composition for coenzyme compound NADH.
    [0098] Next, the NADH coenzyme compound composition solution is adsorbed with anhydrous calcium chloride, and after adsorption is complete, PH101 microcrystalline cellulose, aspartame, polyvinylpyrrolidone, and half croscarmellose sodium are added to mix evenly. and sieve on 20 mesh to prepare the granules, then dry again to sieve on 18 mesh to prepare the complete granules. The obtained granules can be filled into an acid resistant capsule DRcaps to obtain an oral capsule preparation of the coenzyme compound NADH; or the remaining magnesium stearate and croscarmellose sodium are added for mixing uniformly and compressed to obtain the oral tablet preparation of the coenzyme compound NADH.
    [0099] 3. Determination for decay
    [0100] 6 pieces of the prepared oral tablet preparation of the coenzyme compound NADH are taken into a 250 ml beaker, and gently shaken by adding 100 ml of water at 20 ± 1 ° C, to record a time through screen No. 2, which is 70 ± 2s. The suspension obtained is filtered through a 0.45 µm microporous membrane to remove the insoluble solid adjuvant, and the particle size is determined to be 30 ± 3 nm.
    [0101] Embodiment 3
    [0102] 1. The formula of the coenzyme NADH compound oral tablet preparation is as follows:
    [0103] sodium salt of coenzyme NADH 3 g
    [0105] L-carnitine tartrate 7 g
    [0107] Isopropyl myristate 15 g
    [0109] Isopropyl Palmitate 15 g
    [0111] Polyoxyethylene castor oil 15 g
    [0113] Pregelatinized starch 25 g
    [0115] Lactose 70 g
    [0117] Microcrystalline cellulose PH102 130 g
    [0119] 70% ethanol 30 g
    [0121] Low substituted hydroxypropyl cellulose 30 g
    [0123] Stevioside 3 g
    [0125] Food flavor 1 g
    [0126] Sodium stearyl fumarate 10 g
    [0128] Total 1000 tablets / granules
    [0129] 2. The preparation method is as follows:
    [0130] Each component is weighed according to the above formula, and isopropyl myristate, isopropyl palmitate, polyoxyethylene castor oil, and coenzyme NADH are added. in a vial to mix evenly to obtain a clear liquid; then the L-camitin is added to stir completely at 37 ° C for 1 hour to completely dissolve, thus obtaining a solution of the composition for coenzyme compound NADH.
    [0131] Next, the NADH coenzyme compound composition solution is adsorbed with pregelatinized starch, and after the adsorption is complete, lactose, PH102 microcrystalline cellulose, stevioside, food flavor, 70% ethanol are added. % and a half low substituted hydroxypropyl cellulose to mix evenly and sieve with 18 mesh to prepare granules, then dry to sieve again with 18 mesh to prepare whole granules. The obtained granules can be filled into an acid resistant capsule DRcaps to obtain an oral capsule preparation of the coenzyme compound NADH; or the remaining sodium stearyl fumarate and low substituted hydroxypropyl cellulose are added to mix evenly and compressed to obtain the oral tablet preparation of the coenzyme compound NADH.
    [0132] 3. Determination for decay
    [0133] 6 pieces of the prepared oral tablet preparation of the coenzyme compound NADH are taken into a 250 ml beaker, and gently shaken by adding 100 ml of water at 20 ± 1 ° C, to record a time through screen No. 2, which is 65 ± 2s. The suspension obtained is filtered through a 0.45 µm microporous membrane to remove the insoluble solid adjuvant, and the particle size is determined to be 27 ± 3 nm.
    [0134] Embodiment 4
    [0135] 1. The formula of the oral tablet preparation of the coenzyme compound NADH is as follows:
    [0136] Coenzyme NADH 10 g
    [0138] L-carnitine 10 g
    [0140] Isopropyl myristate 30 g
    [0142] Polyoxyethylene castor oil 15 g
    [0144] Lactose 110 g
    [0146] Microcrystalline cellulose 110 g
    [0148] 70% ethanol 20 g
    [0149] Cross-linked polyvinylpyrrolidone 30 g
    [0151] Aspartame 3 g
    [0153] Food flavor 2 g
    [0155] Magnesium stearate 10 g
    [0157] Total 1000 tablets / granules 2. The preparation method is as follows:
    [0158] Each component is weighed according to the above formula, and isopropyl myristate, polyoxyethylene castor oil, and coenzyme NADH are added into a vial to mix evenly to obtain a clear liquid; then the L-carnitine is added to stir it completely at 37 ° C for 1 hour so that it dissolves completely, thus obtaining a solution of the composition for coenzyme compound NADH.
    [0159] Next, the solution of the composition for coenzyme compound NADH is adsorbed with lactose, and after the adsorption is complete, the microcrystalline cellulose, aspartame, food flavor, 70% ethanol and a half amount of Cross-linked polyvinylpyrrolidone to mix evenly and sieve on 18 mesh to prepare granules, then dry to sieve again on 18 mesh to prepare whole granules. The obtained granules can be filled into an acid resistant capsule DRcaps to obtain an oral capsule preparation of the coenzyme compound NADH; or the remaining magnesium stearate and cross-linked polyvinylpyrrolidone are added to mix evenly and compressed to obtain the oral tablet preparation of the coenzyme compound NADH.
    [0160] 3. Determination for decay
    [0161] 6 pieces of the prepared oral tablet preparation of the coenzyme compound NADH are taken into a 250 ml beaker, and gently shaken by adding 100 ml of water at 20 ± 1 ° C, to record a time through screen No. 2, which is 57 ± 2s. The suspension obtained is filtered through a 0.42 µm microporous membrane to remove the insoluble solid adjuvant, and the particle size is determined to be 25 ± 3 nm.
    [0162] Embodiment 5
    [0163] Comparative experimental study in the pharmacological evaluation of mice. Test subject:
    [0164] Fifty male mice are selected at 6 weeks of age. They are fed basal feed for two weeks before the start of the experiment, and the initial body weight is 26 ± 2 g.
    [0165] Group:
    [0166] All the experimental groups were randomly divided into 5 groups of 10 each, and the groups were as follows.
    [0167] Obesity experiment group: 1 group; @ obesity experiment group: 2 groups; @ obesity control group;
    [0168] © obesity target group; © normal white group
    [0169] Establishing the mouse model:
    [0170] Feeding cage, 5 in 1 cage; ambient temperature of 22 ± 2 ° C, humidity of 45 ~ 65%; the illumination of the light is alternated for 12 hours, and the mice are free to eat and drink. Among them, the normal white group is fed normal food, and the other 4 groups are fed high-fat food; changes in body weight are recorded twice a week; the feeding process takes 6 weeks to establish the model.
    [0171] Administration method:
    [0172] Group © receives a solution of the coenzyme compound composition NADH prepared in Embodiment 1 by gavage once a day;
    [0173] Group @ receives a mixture of coenzyme NADH and L-carnitine in Embodiment 1 (without other ingredients) by gavage once a day;
    [0174] The group @ receives L-carnitine by gavage once a day;
    [0175] the amount of administration for Group ©, Group @ and Group @ is 50 mg according to L-carnitine;
    [0176] During the period, 5 groups of mice were fed normal diet on the free diet, and continued to be observed for 4 weeks.
    [0177] Experimental results:
    [0178] At the end of the experiment, the mice are weighed and dissected, then the fat around the liver, kidney, and testes is weighed to calculate the average body weight gain rate of each group of mice (% rate of weight gain = weight gain / experimental initial weight * 100) and average body fat rate (% body fat rate = (weight of fat around the kidney weight of fat around the testes) / body weight after the test * 100) . The experimental results are shown in Table 1.
    [0179] Table 1
    [0181]
    [0184] Embodiment 6
    [0185] In vitro release detection
    [0186] Oral tablet preparations of the coenzyme compound NADH prepared in Embodiments 1 to 4 are respectively taken for sampling at 1 hour, 3 hours, 6 hours, 8 hours, 12 hours at 100 rpm in an acid release medium at 37 ± 0.1 ° C, pH 1.0; then, the cumulative release percentage is calculated by high performance liquid chromatography, and a release profile is plotted in figure 1, where the release time (h) is plotted on the abscissa, and the cumulative release percentage ( %) is plotted on the ordinate.
    [0187] Embodiment 7
    [0188] Electron microscopy
    [0189] The oral tablet preparation of the coenzyme compound NADH prepared in Embodiment 1 is placed in 100 ml of purified water and stirred with a glass rod for 5 minutes; then, the supernatant is centrifuged at 5000 rpm to obtain a supernatant having an opalescence, which is examined by electron microscopy, and an electron micrograph is shown in figure 2.
    [0190] Embodiment 8
    [0191] Stability comparison
    [0192] The oral tablet preparation of the coenzyme compound NADH prepared in Embodiment 1 and the commercially available ENADA® product are placed at 40 ° C and 75% humidity to analyze stability, and sampling of the experimental samples is performed at 0, 1,2, and 3 months, respectively, the experimental results are shown in Table 2.
    [0193] Table 2
    [0194]
    权利要求:
    Claims (10)
    [1]
    A composition for a coenzyme compound NADH, comprising the following components in parts by weight: a coenzyme NADH or a physiologically acceptable salt thereof; and an L-carnitine or a physiologically acceptable salt thereof.
    [2]
    2. The composition for NADH compound according to claim 1, characterized in that the composition comprises the following components in parts by weight: 1 to 10% of a coenzyme NADH or a physiologically acceptable salt thereof, 1 to 10% of an L-carnitine or a physiologically acceptable salt thereof, about 5 to about 50% of an oil phase, about 20 to about 70% of an emulsifier, and about 0 to about 50% of a co-emulsifier.
    [3]
    The composition for the coenzyme compound NADH according to claim 2, characterized in that the oily phase is selected from at least one of soybean oil, ethyl oleate, isopropyl myristate, isopropyl palmitate, corn oil, oil of castor, caprylic / capric triglyceride, glycerol mono oleate, oleic acid, olive oil, sesame oil, peanut oil, and almond oil.
    [4]
    4. The composition for a coenzyme compound NADH according to claim 2, characterized in that the emulsifier is a non-ionic surfactant.
    [5]
    5. The composition for a coenzyme compound NADH according to claim 4, characterized in that the emulsifier is selected from at least one of polyoxyethylene castor oil, hydrogenated polyoxyethylene castor oil, polyethylene glycol-15 stearate, oleic acid, polyethylene glycol, glyceride , polyethylene glycol octyl phenyl ether, octanoic acid, capryl caproyl macrogolglycerides, polosham 188, polysorbate 80, liquid lecithin, sucrose laurate, sucrose palmitate, sucrose stearate, polyethylene glycol, glyceride and glycerol-75 polyethylene glyceride, polysorbate 75
    [6]
    6. The composition for a coenzyme compound NADH according to claim 2, characterized in that the co-emulsifier is selected from at least one of ethanol, propylene glycol, polyethylene glycol 200, polyethylene glycol 400, and isopropanol, 1,2-propanediol, nbutanol, diethylene glycol, monoethyl ether, and propylene carbonate.
    [7]
    7. An oral preparation of coenzyme NADH compound, characterized in that the oral preparation comprises the composition for NADH compound according to any one of claims 1 to 6, and wherein the oral preparation is a tablet preparation or a capsule preparation .
    [8]
    8. The oral preparation of the coenzyme compound NADH according to claim 7, characterized in that the oral preparation further comprises a pharmaceutical excipient, and the pharmaceutical excipient comprises the following components in parts by weight: about 10 to about 70% of an adsorbent , about 10 to about 80% of a diluent, about 0 to about 10% of an adhesive, about 5 to about 10% of a disintegrator, about 0 to about 3% of a flavoring agent, and about 0.5 to about 4% of a lubricant; a weight ratio of the pharmaceutical excipient to the NADH compound composition of from about 20: 1 to about 5: 2.
    [9]
    9. The composition for a coenzyme compound NADH according to any of claims 1 to 6 or an application of the oral preparation of a NADH compound according to claim 7 or 8 to prepare a slimming product.
    [10]
    10. A method for slimming, characterized in that a physiologically acceptable amount of the composition for coenzyme compound NADH according to any of claims 1 to 6 is administered to a slimming agent or a physiologically acceptable amount of the oral preparation of compound of NADH according to claim 7 or 8 to a slimming agent.
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    同族专利:
    公开号 | 公开日
    US20200121709A1|2020-04-23|
    CN109496154A|2019-03-19|
    ES2786774R1|2020-10-16|
    US10894059B2|2021-01-19|
    CN109496154B|2021-07-06|
    WO2019119445A1|2019-06-27|
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    申请号 | 申请日 | 专利标题
    PCT/CN2017/118093|WO2019119445A1|2017-12-22|2017-12-22|Nadh compound, and formulation and application thereof|
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