CN113116898A - Composition containing levocarnitine or acetyl levocarnitine and yohimbine with weight losing function and application thereof - Google Patents

Composition containing levocarnitine or acetyl levocarnitine and yohimbine with weight losing function and application thereof Download PDF

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Publication number
CN113116898A
CN113116898A CN202110426422.5A CN202110426422A CN113116898A CN 113116898 A CN113116898 A CN 113116898A CN 202110426422 A CN202110426422 A CN 202110426422A CN 113116898 A CN113116898 A CN 113116898A
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levocarnitine
pharmaceutically acceptable
acceptable salt
yohimbine
pharmaceutical composition
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安明
况斌
高峥
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Beijing HRDX Medicinal Technologies Co.,Ltd.
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Beijing Tianxibao Technology Co ltd
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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

The invention provides a pharmaceutical composition for losing weight and reducing fat, a preparation method of the pharmaceutical composition and application of the composition in a process of losing weight and reducing fat. The composition comprises (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof and (ii) yohimbine or a pharmaceutically acceptable salt thereof. The composition has the effects of losing weight and reducing weight and body fat.

Description

Composition containing levocarnitine or acetyl levocarnitine and yohimbine with weight losing function and application thereof
Technical Field
The invention belongs to the field of preparations, and particularly relates to a pharmaceutical composition containing (i) levocarnitine or acetyl levocarnitine or pharmaceutically acceptable salts of the levocarnitine and the acetyl levocarnitine, (ii) yohimbine or pharmaceutically acceptable salts of the yohimbine, and (iii) one or more pharmaceutically acceptable excipients. The invention also provides application of the composition, in particular application of the composition in preparing preparations for reducing body weight and body fat. The invention also provides an application of a preparation containing the composition, in particular to a preparation which can be used for reducing body weight and body fat.
Background
In the modern society, along with the continuous progress of the technological level, the material resources are greatly enriched, the life quality of people is greatly improved, but the accompanying 'rich disease' also rapidly spreads among people. Hyperlipemia, hypertension, diabetes, cardiovascular and cerebrovascular diseases and the like are gradually popularized among people along with the acceleration of life pace, poor lifestyle such as poor eating habits and the like.
Among them, obesity is one of the major causes of high incidence of chronic diseases, and the prevalence of overweight and obesity is rapidly increasing worldwide. According to the world health organization statistics, by 2019, the world 23 presents an overweight or obese state in adults. Meanwhile, researches show that the obesity rate of China is changing remarkably, and the obesity prevalence rate of adults is increased to 14%. Concomitantly, China has become the world with the largest population of obese people. This current situation will cause severe burden on the medical health system of our country. Therefore, it is of great importance to suppress the high prevalence of overweight and obesity rates.
At present, various weight-losing medicines or health-care products exist in the market, but the aim of losing weight is achieved by reducing the intake of fat food and reducing the intake of calories of patients mostly. Recent studies have shown that by controlling the intake of high calorie foods, weight loss can be achieved, but at the expense of the patient's health and physical functioning; meanwhile, the weight loss is easy to relapse, and the final purpose of weight loss cannot be achieved. Therefore, the market is in need of a diet supplement or a medicament with higher safety and lower side effect, which can effectively reduce the weight and the body fat and is used for losing weight or losing weight.
L-carnitine (L-carnitine), also known as L-carnitine, is chemically known as L-beta-hydroxy-gamma-methylbutyrate, a substance of retinoid or amino acid. L-carnitine is a water-soluble substance and has a very important role in mammalian metabolism, particularly the oxidation of fatty acids in mitochondria. In the body, l-carnitine exists in the form of free l-carnitine, acetyl l-carnitine (ALC) and other carnitine esters. Approximately 25% of L-carnitine in the body is biosynthesized ex vivo, and its biosynthesis depends on methionine and lysine in the liver and kidney. Most l-carnitine is ingested from the diet, mainly from red meat and milk.
L-carnitine possesses important cellular functions in mitochondrial and peroxidase metabolism. Beta-oxidation of mitochondrial fatty acids can continue to power cells, especially when carbohydrate supply is reduced after fasting or prolonged exercise. L-carnitine is used as a carrier to transport long-chain fatty acid into mitochondria, and promotes beta-oxidation in mitochondrial matrix and ATP generation. Therefore, when L-carnitine is insufficient or the mitochondrial transport system on which L-carnitine depends is defective, the fatty acid oxidation process is greatly attenuated.
L-carnitine can also improve recycling of coenzyme A (CoA) by transporting short-chain acyl in mitochondria from mitochondria to cytoplasm, thereby increasing the content of free CoA in mitochondria. Thus, a decrease in the l-carnitine content causes an increase in the ratio of acyl-CoA to CoASH, a change which may interfere with other pathways of intermediary metabolism, such as: gluconeogenesis, glycolysis, amino acid catabolism and ketone body production.
The L-carnitine is an amino acid which promotes fat to be converted into energy, can promote fatty acid to enter mitochondria for oxidative decomposition, and can improve the oxidation rate of fat, reduce glycogen consumption and delay fatigue in long-time strong movement.
Yohimbine is an indoquinone alkaloid derived from the bark of the African yohimbine tree and the white tree of south America, the name of which is irrelevant. Yohimbine is a selective alpha-2 adrenergic receptor antagonist that inhibits the alpha subunit and maintains adenylate cyclase activity and effects mediated through the beta receptor, thereby aiding in lipid reduction. In addition, yohimbine itself can reduce fat by increasing epinephrine.
The reaction of yohimbine on athletes is tested by a study, and the body fat is reduced by about 2% in 21 days under the condition of being matched with diet control. Experiments in the general population have also shown that yohimbine can increase endogenous epinephrine, increase the rate of fat burning, and appear to be more effective during exercise.
However, the functional action of the single L-carnitine or yohimbine reduces the weight and the body fat, and the inventor unexpectedly finds that the combination of the L-carnitine and the yohimbine has good pharmacological synergistic action, can play the functions of fat elimination, weight reduction, blood fat reduction, cardiovascular and cerebrovascular protection and the like of the L-carnitine, and can also play the synergistic action together with the yohimbine, and particularly has good synergistic action in the aspects of preventing obesity caused by high-fat diet, reducing the weight and the body fat and the like.
Disclosure of Invention
It is an object of the present invention to provide a composition comprising (i) levocarnitine or a pharmaceutically acceptable salt thereof, or acetyl levocarnitine or a pharmaceutically acceptable salt thereof, (ii) yohimbine or a pharmaceutically acceptable salt thereof, and (iii) one or more pharmaceutically acceptable excipients.
It is another object of the present invention to provide a use of a composition comprising (i) levocarnitine or a pharmaceutically acceptable salt thereof, or acetyl levocarnitine or a pharmaceutically acceptable salt thereof, (ii) yohimbine or a pharmaceutically acceptable salt thereof, and (iii) one or more pharmaceutically acceptable excipients for the manufacture of a formulation for weight loss, weight and body fat reduction.
It is another object of the present invention to provide a process for the preparation of a composition comprising (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof, (ii) yohimbine or a pharmaceutically acceptable salt thereof, and (iii) one or more pharmaceutically acceptable excipients.
In one embodiment of the invention, the composition comprises levocarnitine and yohimbine.
In one embodiment of the invention, the composition comprises acetyl levocarnitine fumarate and yohimbine.
In one embodiment of the invention, the composition comprises levocarnitine fumarate and yohimbine hydrochloride.
In one embodiment of the invention, the composition comprises acetyl levocarnitine fumarate and yohimbine hydrochloride.
The weight ratio of the levocarnitine or the pharmaceutically acceptable salt thereof or the acetyl levocarnitine or the pharmaceutically acceptable salt thereof to the yohimbine or the pharmaceutically acceptable salt thereof in the composition is 1 (calculated as the levocarnitine) and 0.001-0.1 (calculated as the yohimbine).
The weight ratio of the levocarnitine or the pharmaceutically acceptable salt thereof or the acetyl levocarnitine or the pharmaceutically acceptable salt thereof to the yohimbine or the pharmaceutically acceptable salt thereof in the composition is 1 (calculated as the levocarnitine) and 0.002-0.05 (calculated as the yohimbine).
The weight ratio of the levocarnitine or the pharmaceutically acceptable salt thereof or the acetyl levocarnitine or the pharmaceutically acceptable salt thereof to the yohimbine or the pharmaceutically acceptable salt thereof in the composition is 1 (calculated by the levocarnitine) to 0.01 (calculated by the yohimbine).
The weight ratio of the levocarnitine or the pharmaceutically acceptable salt thereof or the acetyl levocarnitine or the pharmaceutically acceptable salt thereof to the yohimbine or the pharmaceutically acceptable salt thereof in the composition is 1 (calculated by the levocarnitine) to 0.005 (calculated by the yohimbine).
The compositions of the present invention may exist in a variety of forms of formulations including, but not limited to, liquid form formulations including injections, oral solutions, suspensions, and solid form formulations; preferably, the liquid form formulation comprises an oral solution; solid preparations include tablet, hard capsule, granule, pill, pellet, soft capsule, dripping pill, dry suspension, and granule; preferably, the solid form preparations include hard capsules, tablets, granules, dry suspensions.
Any pharmaceutically acceptable excipient conventionally used in the art may be added to the composition of the present invention to prepare the formulation forms described above. Such excipients include, but are not limited to, fillers, disintegrants, lubricants, wetting agents, solubilizers, solubilizing agents, stabilizing agents, colorants, binders, glidants, flavoring agents, preservatives, suspending agents, coating materials, flavoring agents, plasticizers, surfactants, and the like.
The test results of the embodiment of the invention show that the composition preparation of the invention does not influence appetite or excretion, and compared with the defect that other weight-reducing medicines on the market have more adverse reactions, the composition preparation of the invention is safer and has no obvious side effect. In addition, compared with the weight-losing medicine in the prior art, the weight-losing medicine achieves the purpose of losing weight by suppressing appetite or blocking the absorption of fat in the intestinal tract and increasing the excretion of fat so as to reduce the heat absorbed by the body, the composition preparation disclosed by the invention effectively inhibits the proliferation of fat cells in the body by increasing the energy metabolism of brown fat cells of the body, and prevents the body from being fat due to the residual energy stored in the fat.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The invention is further illustrated by the following examples, which are not intended to be limiting.
Example 1 preparation of a Dry suspension of a combination of Levocarnitine and yohimbine (1000 bag formula)
Figure BDA0003029696050000051
Figure BDA0003029696050000061
Pulverizing the raw materials and adjuvants, sieving with 200 mesh sieve, and drying by proper method; weighing raw and auxiliary materials according to the formula amount, and directly and uniformly mixing by adopting a physical mixing method, wherein the process is as rapid as possible, and the entrance of moisture is reduced as much as possible; and uniformly filling the uniformly mixed powder into an aluminized bag to obtain the product. EXAMPLE 2 preparation of Acetyllevocarnitine fumarate and yohimbine granules (1000 bag formula)
Figure BDA0003029696050000062
Sieving the raw materials with 80 mesh sieve. Pulverizing sucrose and acacia in high-speed multifunctional pulverizer, sieving with 60 mesh sieve, and sieving other adjuvants with 60 mesh sieve respectively. Weighing hydroxypropyl cellulose according to the prescription amount, adding a proper amount of purified water to dissolve the hydroxypropyl cellulose, and uniformly stirring for later use. Weighing sucrose, dextrin, tragacanth, acacia, acetyl levocarnitine fumarate and yohimbine according to the prescription amount, uniformly stirring in a wet granulator, adding the prepared adhesive, and uniformly stirring to prepare a soft material. Granulating the soft material in a rocking granulator (40 mesh sieve). The granules were dried in a 60 ℃ fluidized bed to a moisture of less than 2%. The dried granules were granulated in a rocking granulator (24 mesh sieve). And (4) subpackaging the granules in a subpackaging machine to obtain the granules.
EXAMPLE 3 preparation of Levocarnitine and yohimbine hydrochloride capsules (2000 capsules formula)
Figure BDA0003029696050000071
Weighing the raw materials and the auxiliary materials according to the prescription amount, sieving the raw materials by a 100-mesh sieve, and respectively sieving the auxiliary materials by a 80-mesh sieve. Mixing levocarnitine, yohimbine hydrochloride, pregelatinized starch, sodium laurylsulfate and magnesium stearate completely. Adjusting the capsule filling machine, controlling the filling quantity difference to be +/-5%, and filling to obtain the capsule.
EXAMPLE 4 preparation of oral liquid of acetyl L-carnitine and yohimbine (1000 prescriptions)
Figure BDA0003029696050000072
Weighing sodium chloride, disodium edetate, saccharin sodium, sodium hydroxybenzoate, sodium hydroxy phenylpropionate, apple powder essence, acetyl levocarnitine and yohimbine hydrochloride in the formula amount, adding the mixture into purified water accounting for 65% of the formula volume, and uniformly stirring. Adding the tromethamine or the sodium hydroxide solution with the prescription amount to adjust the pH value, and adding the purified water to the full amount. Stirring, filtering, filling the filtrate into penicillin bottles, and capping. And (3) placing the filled oral liquid at 121 ℃ for autoclaving for 12 minutes to obtain the oral liquid.
EXAMPLE 5 preparation of chewable tablets of Levocarnitine fumarate and yohimbine hydrochloride (1000-tablet formulation)
Figure BDA0003029696050000073
Figure BDA0003029696050000081
Sieving starch hydrolyzed oligosaccharide with 40 mesh sieve, and sieving levocarnitine fumarate and yohimbine hydrochloride with 80 mesh sieve. Weighing the starch hydrolysis oligosaccharide, the levocarnitine fumarate, the yohimbine hydrochloride and the colloidal silicon dioxide according to the prescription amount, adding the mixture into a three-dimensional motion mixer, mixing for 20min, and sieving with a 24-mesh sieve for 2 times after mixing to obtain mixed particles. Adding the magnesium stearate with the prescription amount and mixing for 3-5 min. Tabletting with a tabletting machine to obtain the tablet.
Biological Experimental example 1 Effect of the composition of the present invention on the blood lipid index of mice
Preparation of a sample solution:
orlistat (sample 1): an appropriate amount of orlistat was dissolved in a small amount of DMSO and diluted with physiological saline to make 1ml of a solution containing 7.8 mg.
Levocarnitine (sample 2): an appropriate amount of the solution was diluted with physiological saline to prepare 1ml of a solution containing 65 mg.
Yohimbine (sample 3): an appropriate amount of the extract was diluted with physiological saline to prepare 1ml of a solution containing 0.325 mg.
Composition (sample 4): an appropriate amount of the fine powder of the chewable tablets in the embodiment 5 of the invention is diluted by normal saline to prepare solutions of 0.1625mg yohimbine and 32.5mg levocarnitine fumarate (calculated by levocarnitine) in each 1 ml.
Establishing and grouping a test animal obesity model: after the mice are adaptively fed for two days by using a common feed, 8 mice are selected from 48 mice as normal control groups according to the principle that the total body weight of the mice is consistent, and the rest 40 mice are modeled. The normal group is fed with basal feed, and the rest are fed with high-fat feed until the obesity judgment standard of the mice is reached. During the modeling period, mice were free to ingest drinking water. The weight of the mice was weighed every 5 days and the daily food intake was recorded, and the weight change and growth were observed. Whether the molding is successful is judged by (molding group-normal group)/normal group multiplied by 100% > 20% (2018, 2009, Tianfang, etc.). After feeding for 40 days, weighing the weight of the mice, removing mice with failed Model building and injured mice, randomly dividing the obese mice into 5 groups according to the weight, wherein the groups are respectively an obesity Model Control group (Model Control MC), a Positive drug Control group (Positive Control PC), a levocarnitine group, a yohimbine group and a ComPound group (Compound Dose CD) in example 5, and each group comprises 7 mice.
Animal experiments: after the obesity model is initially established, the normal control group is fed with basal feed, and the rest of the obesity model is fed with high-fat feed until the experiment is finished. The mice are fed with the animal at night, therefore, the gavage is selected to be performed at 5:00-6:00 in the afternoon, the gavage is performed according to the body weight, the volume of each gavage is 200 mu l, and the gavage of a normal group and an obesity model control group is performed with the same volume of normal saline. Weighing once every 3 days for the first time of gavage to adjust the gavage dosage in time, continuously gavage for 28 days, and then taking blood and dissecting the mice. During the period, the mice freely eat drinking water, and the physical sign change of the mice is observed during gastric lavage.
During the molding and the gavage, the weight of the mice is weighed every 5d and the food intake is recorded so as to observe the growth condition of the mice, and the average value of the food intake of each group of mice is calculated every 20d for analysis. After 28 days of gastric lavage, fasting is carried out for 12 hours, 10% chloral hydrate is injected into the tail, and blood is collected in the orbit after the mice are anesthetized. Standing the blood at room temperature for 1h, placing in a refrigerator at 4 deg.C for 30min, centrifuging at 4000r/min for 15min, collecting serum, and determining Triglyceride (TG), Total Cholesterol (TC), high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) contents in the serum according to the kit. The mice are sacrificed by the neck-breaking method, are laid flat on the back, and the length from the tip of the nose to the anus of the mice is accurately measured by a ruler, namely the body length. The Lee's index is calculated as follows (Pinz Lou n-Garc i et al.2018; Bernardis 1970). The calculation formula is as follows:
lee's index (BW)1/3 × 103/BL, where BW is body weight/g; BL is body length/cm.
Statistical analysis: the test results are expressed as mean ± standard deviation (X ± SD), and the statistical analysis of data was performed using IBM SPSS Statistics 20.0, and the data was analyzed using one-way anova combined with least significant difference test (lsd. test), with a statistical significance level P < 0.05.
Weight change (g) and Lee's index (n ═ 7) for mice in each gavage group
Figure BDA0003029696050000101
Note: indicates that P <0.05 difference was significant compared to normal control group, indicates that P <0.01 was very significant; # indicates a significant difference of P <0.05 compared to the obesity model control group, # # indicates a very significant P < 0.01; + indicates a significant difference with P <0.05 and, + + indicates a very significant P <0.01 compared to the levocarnitine group; -represents a significant difference of P <0.05 compared to the yohimbine group, -represents a very significant difference of P <0.01
Before gastric lavage, the body weights of mice in an obesity model group, a positive control group, a levocarnitine group, a yohimbine group and a test group of the composition group in the embodiment 5 are all larger than those of a normal control group, and are statistically different from the normal group, and the difference is very obvious (P < 0.01). After 28 days of gastric lavage, the body weight of the obesity model group is normally increased, the body weights of the other groups of the gavage test groups are reduced to different degrees, and the body weights of the mice in each gavage group before and after gastric lavage are compared, so that the body weight of the composition in the example 5 is reduced most, the positive drug group, the levocarnitine group and the yohimbine group are reduced to different degrees, the weight reducing effect of the gavage composition on the mouse is larger than that of the positive fat reducing drug orlistat, and the fat reducing effect of the compound composition of the levocarnitine and the yohimbine in the composition in the example 5 is obviously stronger than that of each single component. It was also observed that the Lee's index was substantially identical (P > 0.05) for the composition group and the normal control group. The test results show that the two components of the composition have better synergistic weight-losing and lipid-lowering effects.

Claims (11)

1. A pharmaceutical composition comprising:
(i) l-carnitine or a pharmaceutically acceptable salt thereof, or acetyl L-carnitine or a pharmaceutically acceptable salt thereof;
(ii) yohimbine or a pharmaceutically acceptable salt thereof, and
(iii) one or more pharmaceutically acceptable excipients.
2. The pharmaceutical composition according to claim 1, wherein the weight ratio of (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof and (ii) yohimbine or a pharmaceutically acceptable salt thereof is 1 (calculated as levocarnitine) to 0.001-0.1 (calculated as yohimbine).
3. The pharmaceutical composition according to claim 1, wherein the weight ratio of (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof and (ii) yohimbine or a pharmaceutically acceptable salt thereof is 1 (calculated as levocarnitine) to 0.002-0.05 (calculated as yohimbine).
4. The pharmaceutical composition according to claim 1, wherein the weight ratio of (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof and (ii) yohimbine or a pharmaceutically acceptable salt thereof is 1 (calculated as levocarnitine) to 0.002-0.01 (calculated as yohimbine).
5. The pharmaceutical composition according to claim 1, wherein the weight ratio of (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof and (ii) yohimbine or a pharmaceutically acceptable salt thereof is 1 (calculated as levocarnitine) to 0.005 (calculated as yohimbine).
6. Use of a pharmaceutical composition according to any one of claims 1-5 for the preparation of a dietary supplement with weight loss functionality.
7. Use of a composition according to any one of claims 1-45 in the manufacture of a medicament having weight loss properties.
8. Pharmaceutical composition according to any one of claims 1 to 5, characterized in that it is present in a liquid form formulation or a solid form formulation.
9. The pharmaceutical composition of claim 7, wherein the liquid form preparation comprises injection, oral solution, suspension, and the solid form preparation comprises tablet, hard capsule, granule, pill, pellet, soft capsule, drop pill, dry suspension, or granule.
10. The pharmaceutical composition of claim 8, wherein the liquid form formulation comprises an oral solution and the solid form formulation comprises a hard capsule, a tablet, a granule, a dry suspension.
11. A process for the preparation of a pharmaceutical composition according to claim 7 comprising mixing in proportions (i) levocarnitine or a pharmaceutically acceptable salt thereof or acetyl levocarnitine or a pharmaceutically acceptable salt thereof and (ii) yohimbine or a pharmaceutically acceptable salt thereof; adding pharmaceutically acceptable excipient; mixing uniformly and making into solid or liquid preparation.
CN202110426422.5A 2021-04-20 2021-04-20 Composition containing levocarnitine or acetyl levocarnitine and yohimbine with weight losing function and application thereof Pending CN113116898A (en)

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