CN101417119A - Pharmaceutical composition and package for rapidly reducing uric acid in blood and application of anserine to rapidly reducing uric acid in blood - Google Patents

Abstract

The invention relates to a pharmaceutical composition for rapidly reducing uric acid content in blood of an individual, comprising anserine in an amount of more than 50mg to about 600 mg. The invention further relates to a package comprising a pharmaceutical composition having anserine and a label and/or insert indicating that the composition is administered to a subject to provide anserine in an amount greater than 50mg to about 600mg per dose. Furthermore, the present invention relates to the use of anserine in the manufacture of a medicament for rapidly reducing uric acid content in blood of an individual, wherein the medicament comprises anserine in an amount of from greater than 50mg to about 600 mg.

Description

Pharmaceutical composition and packaging for rapidly reducing uric acid in blood and use of anserine for rapidly reducing uric acid in blood

technical field

The present invention relates to the administration of anserine in an amount of greater than 50 mg to about 600 mg to rapidly reduce the level of uric acid in the blood of an individual.

Background technique

Uric acid is the final product of purine metabolism in the human body. The level of uric acid in the blood varies with the balance between the breakdown of purines and the rate of uric acid excretion. Hyperuricemia has been associated or considered identical to gout for several years, but uric acid has now been identified as a marker of a number of metabolic and hemodynamic abnormalities. High uric acid levels in the blood induce gout and are often associated with symptoms such as muscle cramps, localized swelling, inflammation, joint pain, muscle fatigue, pressure, and myocardial infarction.

Various commercially available drugs have been used to treat gout, such as Benzbromarone (URINORM), Probenecid, Allopurinol, Bucolome, Cinchophan, and Colchicum Alkali (Colchicine). These drugs work by, for example, inhibiting uric acid formation, removing excess uric acid, acting on the kidneys to aid in the elimination of uric acid, inhibiting the activity of xanthine oxidase to convert xanthine to uric acid, and accelerating uric acid excretion. However, these drugs are known to be hepatotoxic and cause various side effects such as urinary stones, gastrointestinal obstruction, jaundice and anemia. These drugs have not been reported to be able to rapidly lower uric acid levels in an individual's blood.

Some dipeptides are known to be useful in reducing uric acid levels in the blood. For example, ROC (Taiwan) Patent No. I280136 (ROC (Taiwan) Patent Application No. 092114798) discloses a composition for reducing uric acid in an individual, which comprises an effective amount of one or more A dipeptide consisting of or its functional equivalent and alanine or its functional equivalent. Exemplary dipeptides mentioned in the ROC patent include carnosine, anserine, carcinine, and ophidine. It only teaches oral administration of the composition to provide the dipeptide in an amount of about 8 mg to about 50 mg, preferably about 10 mg to about 45 mg per day, but does not disclose or suggest any route by which the dipeptide can be rapidly reduced in the blood of an individual .

Anserine (β-alanyl-1-methyl-L-histidine) is a highly stable dipeptide with a pK value of about 7.1 and remains intact at low pH (<3.0). Anserine occurs naturally in skeletal muscle and brain tissue of vertebrates and is formed by a peptide bond between β-alanine and 1-methyl-L-histidine (see Tolkachevskaya ), NF.1929. Journal of Physiol Chemistry (Z Physiol Chem.) 185:28-32.). In 1938, it was reported that anserine was an ideal physiological acid-base buffer. Due to its physiological acid-base buffering capacity, anserine effectively eliminates lipid peroxidation promoted by changing the pH value of biological systems. For acidemic individuals suffering from gout, the administration of anserine, which acts as an acid-base buffer, helps to adjust the pH value of the blood and is beneficial to reduce the uric acid content in the blood. It will be appreciated that 40% of the cushioning capacity of fast-twitch muscle fibers is provided by dipeptides in the mobile phase, while the remainder is provided by myosin, which is substantially in the stationary phase (see Bate-Smith). -Smith), EC.1938, "The buffering of muscle in rigour: protein, phosphate and carnosine.," Journal of Physiology (J Physiol.) 92:336-43.) . This suggests that in highly structured myocytes, the local acid-base gradient is composed of buffer assistance by the mobile phase and buffer inhibition by the stationary phase.

In addition, anserine has various antioxidant properties and is useful as a free radical scavenger or metal chelator. Individuals with chronic inflammation often have higher concentrations of free radicals in vivo. Administration of anserine, which acts as a free radical scavenger, facilitates the elimination of free radicals.

Anserine is also effective in inhibiting lipid peroxidation promoted by iron, hemoglobin, lipid peroxidase and singlet oxygen (see Babizhayev MA et al., 1994, "L-carnosine (β- Alanyl-L-histidine) and decarboxylated carnosine (β-alanylhistamine) act as natural antioxidants (L-carnosine (beta-alanyl-L -histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities), "Biochem J. 304 (Pt2): 509-516 and Kohen R. .) et al., 1988, "Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain," Proceedings of the National Academy of Sciences (Proc. Natl Acad Sci USA.) 85(9): 3175-3179.).

In addition, anserine can improve the oxidative stress in the living body caused by fatigue, and enhance the oxygen free radical absorption capacity in the living body. Anserine may also act as a precursor of transmitters in the central histaminergic nervous system. Through the metabolism of histidine contained in anserine, anserine can effectively adjust the concentration of histamine in the central nervous system, reduce the concentration of cortisol in the blood and relieve fatigue (see Aoi W (Aoi W.) et al. , 2006, "Exercise and functional foods.," Nutr J. 5: 15-22 and US Patent No. 6,680,294).

However, no commercially available drug containing anserine for the treatment of gout has been reported to have the efficacy of rapidly reducing the level of uric acid in the blood of an individual.

There remains a need to develop a new drug that can rapidly reduce the level of uric acid in the blood of an individual, thereby treating gout and alleviating the symptoms associated with high levels of uric acid in the blood.

Contents of the invention

The present inventors have surprisingly found that administration of anserine in an amount of greater than 50 mg to about 600 mg per dose rapidly reduces the level of uric acid in the blood of an individual.

Accordingly, the present invention relates to a pharmaceutical composition for rapidly reducing the level of uric acid in the blood of an individual comprising anserine in an amount greater than 50 mg to about 600 mg.

The invention further relates to a package comprising a pharmaceutical composition of the invention and a label and/or package insert indicating that the composition is to be administered to an individual to provide anserine in an amount of greater than 50 mg to about 600 mg per dose.

Furthermore, the invention relates to a method for rapidly reducing the level of uric acid in the blood of an individual comprising administering to the individual anserine in an amount from greater than 50 mg to about 600 mg.

Furthermore, the present invention relates to the use of anserine in the manufacture of a medicament for rapidly reducing the level of uric acid in the blood of an individual, wherein said medicament comprises anserine in an amount of greater than 50 mg to about 600 mg.

Description of drawings

Figure 1 shows the effect of orally administered anserine on the uric acid content in blood.

Detailed ways

In a first aspect, the present invention provides a pharmaceutical composition for rapidly reducing uric acid levels in the blood of an individual comprising anserine in an amount greater than 50 mg to about 600 mg. The pharmaceutical composition of the present invention can quickly reduce the uric acid content in the blood of an individual, thereby treating gout and/or improving symptoms associated with high blood uric acid content.

In a second aspect, the invention provides a package comprising a pharmaceutical composition of the invention and a label and/or package insert indicating that the composition is to be administered to an individual to provide anserine in an amount of greater than 50 mg to about 600 mg per dose . The pack of the present invention is suitable for rapidly reducing the level of uric acid in the blood of an individual, thereby treating gout and/or ameliorating symptoms associated with high levels of uric acid in the blood.

In a third aspect, the invention provides a method for rapidly reducing uric acid levels in the blood of an individual comprising administering to the individual anserine in an amount from greater than 50 mg to about 600 mg. The methods of the present invention rapidly reduce the level of uric acid in the blood of an individual, thereby treating gout and/or ameliorating symptoms associated with high levels of uric acid in the blood.

In a fourth aspect, the present invention provides a use of anserine in the manufacture of a medicament capable of rapidly reducing uric acid levels in the blood of an individual, wherein the medicament comprises anserine in an amount greater than 50 mg to about 600 mg. The medicament rapidly reduces the level of uric acid in the blood of an individual, thereby treating gout and/or ameliorating symptoms associated with high levels of uric acid in the blood.

Anserine may be naturally occurring anserine or synthetic anserine. In the present invention, anserine is administered to individuals in an amount greater than 50 mg to about 600 mg, preferably about 100 mg to about 500 mg, more preferably about 150 mg to 250 mg per dose, so as to achieve the effect of rapidly reducing the uric acid content in the blood of the individual.

In the present application, the term "rapidly reducing the uric acid content in the blood" means that within 1 hour of administering anserine, the reduction of the uric acid content in the individual's blood is about 0.5 to about 4 mg/dL. The term "individual" refers to a mammal, preferably a human. In addition, the term "symptoms associated with high uric acid content" refers to, for example, muscle spasm, local swelling, inflammation, joint pain, muscle fatigue, feeling of pressure, myocardial infarction, or a combination thereof.

The pharmaceutical compositions and medicaments of the present invention may be prepared by any conventional method known in the art. In addition to the active ingredient anserine, the pharmaceutical composition and medicine of the present invention may also contain pharmaceutically or physiologically acceptable excipients. Suitable pharmaceutically acceptable excipients include, but are not limited to, dextrin-maltose, lactose, sucrose, mannitol, starch, microcrystalline cellulose, carboxymethylcellulose, talc and magnesium stearate .

The pharmaceutical compositions and medicaments of the present invention can be formulated into appropriate dosage forms, such as tablets, powders, granules, capsules, liquids and suspensions, for various administration routes. The pharmaceutical compositions and medicaments of the invention may be administered via any suitable route, preferably oral or parenteral.

Any known packaging and printing methods may be used to prepare the packaging of the present invention.

example

The invention will become apparent with reference to the following examples, which are purely illustrative and should not be used to limit the scope of the invention as described in the claims.

Example 1

Anserine (GL Biochem Ltd., Shanghai, China) and dextrin-maltose were filled into gelatin capsules (total weight 400 mg), and the capsules contained 50 mg anserine. Individuals suffering from gout who have high levels of uric acid in the blood take 3 capsules (total anserine 150 mg) twice a day and 5 capsules once on the same day (total anserine 250 mg), so the individual takes daily The total dose of anserine is 550mg. The uric acid content in the blood was monitored by UroSpeed (a rapid serum-uric acid test strip, Apex Biotechnology Co., Inc., Hsinchu, Taiwan, ROC). The results are shown in Table 1 and further graphically shown in Figure 1 .

Table 1: Decrease in blood uric acid level 1 hour after oral administration of anserine

As shown in Table 1 and Figure 1, the decrease in blood uric acid levels ranged from 0.9 mg/dL to 1.5 mg/dL 1 hour after taking the capsules containing anserine. One hour after taking 150 mg of anserine at 10:35, the level of uric acid in the blood was reduced by 1.5 mg/dL. After the subject consumed beef noodles at noon, the uric acid level in the subject's blood increased to 11.9 mg/dL. One hour after taking 150 mg anserine at 13:15, the uric acid content in the blood of the individual decreased by 0.9 mg/dL. One hour after taking 250mg anserine at 17:17, the uric acid content in the individual's blood decreased by 1.3mg/dL. The data presented in Table 1 demonstrate that administration of anserine rapidly reduces the uric acid level in the blood of an individual within 1 hour.

Example 2

In this oral administration test, 15 voluntary adult subjects (9 males and 6 females aged 28 to 53) suffering from chronic hyperuricemia were tested. The individual discontinued their normal medication for at least 3 days. The average uric acid level in the blood of the individual is greater than 9.3 mg/dL. The individuals were randomly divided into 5 groups, each group comprising 3 individuals, who took the following doses of anserine respectively: 50 mg, 100 mg, 150 mg, 200 mg and 250 mg. After 1 hour, the level of uric acid in the individual's blood was measured. The uric acid level in his blood was found to decrease by 1.1 mg/dL to 1.3 mg/dL. Among the 5 groups, the group taking 150 mg of anserine had the most significant reduction in blood uric acid levels. The results are shown in Table 2.

Table 2: Effects of 1 hour after oral administration of various doses of anserine on the uric acid content in blood

Claims (14)

1. medical composition that is used for reducing fast the uric acid content of individual blood, it comprises the anserine to the amount of about 600mg greater than 50mg.

2. medical composition as claimed in claim 1, it comprises the anserine of about 100mg to the amount of about 400mg.

3. medical composition as claimed in claim 2, it comprises the anserine of the amount of about 150mg to 250mg.

4. as the described medical composition of arbitrary claim in the claim 1 to 3, its be applicable to the treatment gout and/or alleviate with blood in the relevant symptom of metabolic arthritis content.

5. medical composition as claimed in claim 4, wherein said symptom are selected from muscle spasm, local swelling, inflammation, arthralgia, muscle fatigue, constriction, myocardial infarction and its combination.

6. packing, it comprises:

The medical composition that comprises anserine; With

Indication throws with individual described compositions providing each dosage greater than the anserine of 50mg to the amount of about 600mg, so that treat gout and/or alleviate the label and/or the inset of the symptom relevant with metabolic arthritis content in the blood.

7. packing as claimed in claim 6, wherein said label and/or the indication of described inset throw with individual described compositions so that about 100mg to be provided the anserine to the amount of about 500mg.

8. packing as claimed in claim 7, wherein said label and/or the indication of described inset throw with individual described compositions so that about 150mg to be provided the anserine to the amount of about 250mg.

9. packing as claimed in claim 6, wherein said symptom are selected from muscle spasm, local swelling, inflammation, arthralgia, muscle fatigue, constriction, myocardial infarction and its combination.

10. an anserine is being made in order to the purposes in the medicine of the uric acid content in the quick reduction individual blood, and wherein said medicine comprises the anserine to the amount of about 600mg greater than 50mg.

11. purposes as claimed in claim 10, wherein said medicine comprise the anserine of about 100mg to the amount of about 400mg.

12. purposes as claimed in claim 11, wherein said medicine comprise the anserine of about 150mg to the amount of about 250mg.

13. purposes as claimed in claim 10, wherein said medicine be applicable to the treatment gout and/or alleviate with blood in the relevant symptom of metabolic arthritis content.

14. purposes as claimed in claim 13, wherein said symptom are selected from muscle spasm, local swelling, inflammation, arthralgia, muscle fatigue, constriction, myocardial infarction and its combination.

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