[19] STATE INTELLECTUAL PROPERTY OFFICE OF THE P.R.C
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`
`
`[51] Int. Cl.
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`C07C 279/14 (2006.01)
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`C07C 277/00 (2006.01)
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`
`
`
`
`[12] Publication Description for Invention Patent Application
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`[21] Application No.: 200710059839.2
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`[43] Date of Publication: April 15, 2009 [11] Publication No.: CN 101407478A
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`[74] Patent Agency: Zongxin Patent and
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`Trademark Agency Co., Ltd. of Tianjin City
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` Attorney: LIU Ying
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`
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`Claims: 1 page; Description: 2 pages
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`
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`[22] Application Date: 2007.10.12
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`[21] Application No.: 200710059839.2
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`[71] Applicant: Tianjin Tiancheng Pharmaceutical
`
`Co., Ltd.
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`Address: No. 9, Yangliuqing Liuming Road,
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`Xiqing District, Tianjin City, 300380
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`[72] Inventor: ZHANG Guoji
`
`
`
`[54] Title:
`
`METHOD FOR PREPARING CREATINE
`
`HYDROCHLORIDE
`
`[57] Abstract
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`The present invention relates to a method for
`
`preparing creatine hydrochloride, which belongs to a
`
`method for preparing guanidine or derivatives
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`thereof, wherein hydrochloric acid and creatine
`
`monohydrate are reacted at a temperature from 25 to
`
`40°C,
`
`then
`
`the mixture
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`is concentrated after
`
`filtration, and the crystal is separated, washed with
`
`ethanol and dried, so as then to produce a finished
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`product of creatine hydrochloride.
`
`
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`
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`001
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`

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`200710059839.2
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`CLAIMS
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`1/1
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`1. A method for preparing creatine hydrochloride, characterized in that, hydrochloric acid
`
`and creatine monohydrate are reacted at a temperature from 25 to 40°C, then the mixture is
`
`concentrated after filtration, and the crystal is separated, washed with ethanol and dried, so
`
`as to produce creatine hydrochloride.
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`2. The method for preparing creatine hydrochloride according to claim 1, characterized in
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`that, hydrochloric acid and creatine monohydrate have a molar ratio of 1 : 1.
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`3. The method for preparing creatine hydrochloride according to claim 1, characterized in
`
`that, the solution after the reaction has a pH value of 1.
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`4. The method for preparing creatine hydrochloride according to claim 1, characterized in
`
`that, hydrochloric acid employed in the reaction has a concentration of 30%.
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`5. The method for preparing creatine hydrochloride according to claim 1, characterized in
`
`that, the concentration condition includes a vacuum degree of 0.09 Mpa, and a temperature
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`of 40°C to 50°C.
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`6. The method for preparing creatine hydrochloride according to claim 1, characterized in
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`that, ethanol employed for the washing is anhydrous ethanol, in an amount of 0.2 time the
`
`creatine hydrochloride after separation and spin-drying.
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`7. The method for preparing creatine hydrochloride according to claim 1, characterized in
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`that, the drying temperature is from 50°C to 60°C.
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`1
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`200710059839.2
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`DESCRIPTION
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`1/3
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`METHOD FOR PREPARING CREATINE HYDROCHLORIDE
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`TECHNICAL FIELD
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`The present invention relates to a method for preparing guanidine or derivatives
`thereof, in particular to a method for preparing creatine hydrochloride.
`
`BACKGROUND ART
`
`Creatine is an amino acid synthesized from three amino acids that are arginine,
`glycine and methionine. Creatine can be used in the treatment of patients with Parkinson's
`disease and Alzheimer's disease, as well as in the treatment of muscular degeneration in the
`elderly. It is also a nutritious supplement for muscle building. The efficacy of creatine
`supplements have been recognized and accepted. Such products have effects of improving
`muscular performance and enhancing muscle strength. At present, there exists a need for
`derivatives thereof in an amount of about 5000 to 6000 tons per year around the world. As
`a result of poor water solubility of creatine, a substantial amount of water must be ingested
`to absorb sufficient amount of creatine to the human body, and thus the absorption is
`greatly limited in case of oral administration. In order to overcome these disadvantages,
`creatine supplements are mostly manufactured into various organic acid salts or inorganic
`acid salts before use.
`
`In previous processes, water is added, in an amount of certain times, into creatine
`monohydrate, and hydrochloric acid is dropped therein, to carry out reaction with stirring.
`The mixture is filtered after completion of the reaction, concentrated under a high vacuum
`condition (not exceeding 50°C), and cooled. The crystal is separated and then washed with
`acetone, and dried to obtain a product.
`
`As a result of a substantial amount of water added, by-product creatinine in the
`reaction will be increased accordingly, allowing the yield and product quality to be
`influenced, and at the same time allowing the concentration time to be increased and the
`whole technological process time to be extended. Due to the relatively high price and
`toxicity of acetone, the production cost is increased, and harm will be caused to the human
`body to a certain extent during the production.
`
`SUMMARY OF THE INVENTION
`
`In the present invention, in order to solve the problems of the long production cycle
`and the toxic material for the production in the prior art, there is provided a method for
`preparing creatine hydrochloride wherein no water is added during the production,
`production cycle is short, product quality is improved, and raw materials for the production
`have lower toxicity.
`
`The present invention employs technical solutions as follows:
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`200710059839.2
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`DESCRIPTION
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`2/3
`
`A method for preparing creatine hydrochloride, wherein hydrochloric acid and
`creatine monohydrate are reacted at a temperature from 25°C to 40°C, then the mixture is
`concentrated after filtration, and the crystal is separated, washed with ethanol and dried, so
`as to produce a finished product.
`
`In the present invention, hydrochloric acid and creatine monohydrate have a molar
`ratio of 1 : 1, and the solution after reaction has a pH value of 1.
`
`Hydrochloric acid employed in the reaction has a concentration of 30%.
`
`The concentration condition includes a vacuum degree of 0.09 Mpa, and a temperature
`of 40°C to 50°C.
`
`Ethanol employed for the washing is anhydrous ethanol, in an amount of 0.2 time the
`creatine hydrochloride after separation and spin-drying.
`
`The drying temperature is from 50°C to 60°C.
`
`In the present invention, the reaction temperature does not exceed 40°C, at the same
`time no substantial amount of water participates in the reaction, and thus side reactions are
`few and the yield is improved.
`
`The concentration process of the present invention employs concentration at high
`vacuum and low temperature, to shorten the concentration time and ensure the product
`quality.
`
`The present invention has advantages and positive effects as follows.
`
`1. Because no water is added in the present invention, the formation of by-product
`creatinine in the reaction is reduced, and the product quality is improved.
`
`2. In the existing process, because a substantial amount of water is added,
`concentration time is longer correspondingly; and also hydrochloric acid is dropped into
`the aqueous creatine solution, therefore the process is time-consuming and the production
`cycle is rather long. In the present invention, no water is added into reactants, thus the
`concentration time is greatly reduced; and the raw materials are charged, at a time, into a
`reaction tank, such that the production cycle is shortened, and efficiency of labor is
`significantly increased.
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`3. Ethanol is used in place of acetone as the washing liquor, to reduce the cost, reduce
`the toxicity, reduce the harm to the human body, and ameliorate the production
`environment.
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`DETAILED DESCRIPTION
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`Detailed illustration of the present invention is given below by particular examples.
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`DESCRIPTION
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`3/3
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`Example 1
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`200 kg of creatine monohydrate and 160 kg of hydrochloric acid at a concentration of
`30% were charged into a 1000-L reaction tank. Stirring was activated. The reaction
`temperature was maintained at 25°C. Creatine monohydrate was dissolved completely. The
`pH value was measured. If the pH value was lower than 1, the solution was adjusted to pH
`1 with hydrochloric acid. After about 30 min, the reaction was terminated, and stirring was
`stopped. The reaction solution was filtered, then charged into a 1000-L crystallizing tank,
`and subjected to moisture removal under a condition of 0.09 Mpa and 50°C temperature for
`concentration. Crystal was occurred in the crystallizing tank at about 1.5 h. The
`temperature was decreased to 25°C, and the crystal was precipitated. The crystal was
`separated and spin-dried with a centrifuge, then washed with anhydrous ethanol accounting
`for 10% by weight of the wet material obtained, and spin-dried. The wet product was
`placed into a drying box, and fan-dried at a temperature of 60°C, so as to obtain creatine
`hydrochloride, at a yield of 85% and a purity of 99%.
`
`Example 2
`
`200 kg of creatine monohydrate and 160 kg of hydrochloric acid at a concentration of
`30% were charged into a 1000-L reaction tank. Stirring was activated. The reaction
`temperature was maintained at 40°C. Creatine monohydrate was dissolved completely. The
`pH value was measured. If the pH value was lower than 1, the solution was adjusted to pH
`1 with hydrochloric acid. After about 20 min, the reaction was terminated, and stirring was
`stopped. The reaction solution was filtered, and then charged into a 1000-L crystallizing
`tank. The reaction solution was subjected to moisture removal under a condition of 0.09
`Mpa and 40°C temperature for concentration. Crystal was occurred in the crystallizing tank
`at about 2 h. The temperature was decreased to 20°C, and the crystal was precipitated. The
`crystal was separated and spin-dried with a centrifuge, then washed with anhydrous ethanol
`accounting for 10% by weight of the wet material obtained, and spin-dried. The wet
`product was placed into a drying box, and fan-dried at a temperature of 50°C, so as to
`obtain creatine hydrochloride at a yield of 85% and a purity of 99%.
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