CN1628650A - Compound diisopropylamine dichloroacetate freeze dried injection and preparation method thereof - Google Patents
Compound diisopropylamine dichloroacetate freeze dried injection and preparation method thereof Download PDFInfo
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- CN1628650A CN1628650A CN 200310111617 CN200310111617A CN1628650A CN 1628650 A CN1628650 A CN 1628650A CN 200310111617 CN200310111617 CN 200310111617 CN 200310111617 A CN200310111617 A CN 200310111617A CN 1628650 A CN1628650 A CN 1628650A
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Abstract
Disclosed is a compound diisopropylamine dichloroacetate freeze dried preparation, which comprises unit dosage of tensicor 10-200mg, sodium gluconate 9.5-200mg, and at least one pharmaceutically acceptable carrier, the carrier comprises excipient, pH modifier, anti-oxidant agent, stabilizer, and is provided in the form of unit amount in the container.
Description
Technical field
The present invention relates to field of medicaments, relate in particular to compound diisopropylamine dichloroacetate freeze-dried powder and preparation method thereof.
Background technology
Compound diisopropylamine dichloroacetate can provide body to synthesize the needed methyl of choline, and choline and fatty liver effect help fat by being transported to outside the liver gathering of minimizing intrahepatic fat in the liver; Can reduce the concentration of glycerol and free fatty in the tremulous pulse, reduce the absorption of liver, suppress the synthetic of liver tg glycerol; Activate pyruvate dehydrogenase complex by suppressing pyruvic dehydrogenase, increase the picked-up of hepatocyte oxygen simultaneously, promote the lactic acid oxidation, reduce lactate level in the blood, improve the acid-base metabolism of body, thereby improve hepatocellular energy metabolism.Detoxifcation, anti-fatty liver arranged, improve liver function, promote the effects such as utilization rate of cell oxygen; And have vasodilator, increase the effect of big cerebral blood flow.Be used for acute and chronic hepatitis, fatty liver, the hepatic insufficiency that early stage liver cirrhosis, other diseases cause; Also be used for the imbalance of peripheral terminals and cerebral blood vessel, improve apoplexy sequela, the auxiliary treatment of diseases such as hypertension.
Yet at present, market has only the liquid drugs injection supply, diisopropylamine dichloroacetate (C
8H
17O
2NCl
2) case of thermal instability, under solution state, decomposing increases, and the diisopropylamine dichloroacetate of liquid drugs injection descends because of content appears in hydrolysis behind the high temperature sterilize, and impurity increases phenomenon, the liquid drugs injection less stable, its storage and transportation are also inconvenient.And liquid drugs injection has only 20mg/1ml, 40mg/2ml specification, and clinical daily diisopropylamine dichloroacetate dosage is at 20-60mg, and the unit dose of the principal agent of this reflection diisopropylamine dichloroacetate liquid drugs injection is on the low side, and on pharmaceutical preparation, its design is unreasonable.Therefore, this not only wastes the doubly above packaging material of 1-2 in many cases, consumes more human resources, is a waste greatly to the wealth of society! And use extremely inconvenient.
Summary of the invention
The objective of the invention is to overcome the deficiency of compound diisopropylamine dichloroacetate liquid drugs injection, invent freeze-dried powder of this compound recipe and preparation method thereof.
Compound diisopropylamine dichloroacetate freeze-dried powder of the present invention, the diisopropylamine dichloroacetate 10-200mg that wherein contains unit dose, preferred 20～60mg, gluconic acid sodium salt 9.5-200mg, preferred 19～57mg, and containing a kind of pharmaceutically acceptable carrier at least, carrier comprises: excipient, pH regulator agent, antioxidant, stabilizing agent etc.; And in container, to provide with unit dosage form.
Pharmaceutically acceptable excipient is a dextran; mannitol; glucose; sorbitol; sucrose; lactose; lactose monohydrate; lactose; trehalose; maltose; xylose; xylitol; glucide; magnesium chloride; sodium chloride; sodium sulfate; succinic acid and salt thereof; sodium hydrogen phosphate; sodium dihydrogen phosphate; gluconic acid and salt; as gluconic acid sodium salt; potassium; calcium; magnesium etc.; glucuronic acid and salt; as D-Glucuronic acid sodium salt; potassium; calcium; magnesium salt etc.; calcium lactobionate.; polyvinylpyrrolidone; cetomacrogol 1000-4000; magnesium sulfate; inositol; phytic acid; imidazoles; nicotiamide; citric acid; citrate; pantothenic acid and salt thereof; as calcium pantothenate; sodium pantothenate; agedoite; glycine; lysine; arginine; methionine; glutamic acid; histidine; histidine; Deng aminoacid and amino acid salts; cholate; as NaGC; NaTDC; sodium taurocholate; sodium cholate; ursodeoxycholic acid sodium etc.; glycyrrhizic acid; enoxolone; glycyrrhetate; glycyrrhizin; glycyrrhetate; glycyrrhetate such as trisodium glycyrrhetinate; disodium salt; three amine salt; two amine salt; monoamine salt; potassium salt; water for injection; gelatin hydrolysate; soluble starch; soluble cellulose class material; as HPMC etc., cyclodextrin or cyclodextrin derivative.Can contain wherein one or more.
Cyclodextrin or cyclodextrin derivative comprise alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, glucityl-cyclodextrin (G
1-CYD), comprise glucosyl group-alpha-cyclodextrin (G
1-α-CYD), glucose group-beta-cyclodextrin (G
1-β-CYD), didextrose group-beta-cyclodextrin (2G
1-β-CYD), malt-base-cyclodextrin (G
2-CYD), malt-base-alpha-cyclodextrin (G
2-α-CYD), malt sugar group-beta-cyclodextrin (G
2-β-CYD), malt-base-gamma-cyclodextrin (G
2-γ-CYD), maltotriose glycosyl-cyclodextrin (G
3-CYD), maltotriose glycosyl-alpha-cyclodextrin (G
3-α-CYD), G 3-(G
3-β-CYD), maltotriose glycosyl-gamma-cyclodextrin (G
3-γ-CYD), methyl beta-schardinger dextrin-, ethyl beta-schardinger dextrin-, dimethyl-, 2,6 dimethyl-s (DM-β-CYD), 2,3,6 trimethyl beta-schardinger dextrin-s (TM-β-CYD), beta-schardinger dextrin-sulfoalkyl ether (SAE-β-CYD), ethoxy beta-schardinger dextrin-, hydroxypropyl, 2-hydroxypropyl (2-HP-β-CYD), 3-hydroxypropyl (3-HP-β-CYD), 2,3-dihydroxypropyl beta-schardinger dextrin-(DHP-β-CYD), cyclodextrin CDPS, CDPS-H, CDPS-L etc.
The wherein preferred glucose of excipient, mannitol, sorbitol, lysine, arginine, sodium chloride, nicotiamide, sodium pantothenate, 2-hydroxypropyl, water for injection.
Pharmaceutically acceptable pH regulator agent can be a hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, hydrobromic acid, formic acid, propanoic acid, acetic acid, potassium acetate, sodium acetate, ammonium acetate, boric acid, lactic acid and salt thereof, as sodium lactate, citric acid and salt thereof, as disodium citrate, the citric acid trisodium, sodium citrate, citric acid monohydrate, potassium citrate, natrium carbonicum calcinatum, sal soda, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, soda-lime, calcium oxide, water for injection, phosphoric acid,diluted, dalcium biphosphate, calcium hydrogen phosphate, calcium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, diammonium phosphate, dipotassium hydrogen phosphate, maleic acid, succinic acid and salt, phytic acid, D-tartaric acid, L (+)-tartaric acid, sodium bitartrate, DL-tartaric acid, potassium hydrogen tartrate, sodium potassium tartrate tetrahydrate, Borax, boric acid, succinic acid, caproic acid, adipic acid, fumaric acid, ammonium carbonate, drikold, liquid CO 2, the aromatic amine fine wine, 1, the 2-hexamethylene diamine, hypophosphorous acid, Polymeric sodium metaphosphate., Kurrol's salt, potassium metaphosphate, Tris, triethanolamine, diethanolamine, ethanolamine, isopropanolamine, diisopropanolamine (DIPA), 2-amino-2-(methylol) 1, ammediol amine, 1, the 2-hexamethylene diamine, N-methyl Fructus Vitis viniferae amine, diisopropylamine and their salt, multi-hydroxy carboxy acid and salt, the multi-hydroxy carboxy acid is a glucuronic acid, gluconic acid, lactobionic acid, lactobionic acid, galacturonic acid, malic acid, threonic acid THREONIC ACID., glucoheptonic acid, two (hydroxymethyl) acetic acid, trihydroxy-butyric acid etc., hydroxyacetic acid, dihydroxy-acid, the dihydroxy butanoic acid, the dihydroxy isovaleric acid, the dihydroxy isopropylformic acid., 2,3-dihydroxy 1,3-propanedicarboxylic acid, the dihydroxy adipic acid, nicotinic acid, concentrated ammonia solution, dilute ammonia solution, carbon dioxide,-gluconic acid lactone, glycyrrhetate, phytic acid (phytic acid) and salt, as sodium phytate, potassium phytate, benzoic acid and salt thereof, as sodium benzoate, methanesulfonic acid, benzenesulfonic acid, p-methyl benzenesulfonic acid, lactobionic acid, glyceric acid, glycine, lysine, arginine, methionine, one or more of aminoacid and amino acid salts.The preferred gluconic acid of PH regulator, hydrochloric acid, sodium hydroxide, citric acid.
Its antioxidant and stabilizing agent can be inorganic sulfide compounds, sulfurous acid, sulfite compound (sodium sulfite, sulfurous acid etc.), bisulfite salt compound (sodium sulfite, Potassium acid sulfite etc.), pyrosulfite (comprises sodium pyrosulfite, potassium metabisulfite etc.), dithionite (sodium salt, potassium salt etc.), thiosulfate (comprises sodium salt, potassium salt etc.), the organosulfur compound thiourea, glutathion, sodium thioglycolate, dimercaptopropanol, BAL, TGA and salt, as sodium thioglycolate etc., sodium sulfoxylate formaldehyde, thioglycerin, 2-mercaptopropionic acid and salt, thio-2 acid and salt, the sulfo-sorbitol, thiosalicylic acid, dithiooxamide, oxine, pyridoxamine and salt, phenol compound, as gallic acid and salt, progallin A, propyl gallate, gallateoctylester, lauryl gallate, caffeic acid, the caffeiate, ferulic acid, ferulate, dibenzylatiooluene, butylated hydroxyarisol, the di-t-butyl Pyrogentisinic Acid, nordihydroguaiaretic acid (NDGA), 2, the 5-resorcylic acid, 2,5-resorcylic acid salt, gluconic acid, phytic acid (phytic acid) and salt, the phenol or derivatives thereof, salicylic acid or its slaine; Amino acids, comprise sodium glutamate, glycine, cysteine, methionine, L-leucine, L-isoleucine, L-tryptophan, L-lysine, L-methionine, L-a word used in person's names propylhomoserin, aminoacid with and salt; Glycyrrhetate, glycyrrhetate, enols used, as ascorbic acid and Ascorbate (comprising sodium ascorbate etc.), ascorbic acid Petiolus Trachycarpi ester, arabo-ascorbic acid and erythorbate, acetone closes ascorbic acid, the a-tocopherol, the L-cysteine, the L-cysteine hydrochloride, nicotiamide, tartaric acid, EDTA and EDTA one sodium, the EDTA disodium, EDTA four sodium, calcium disodium edetate, divinyl triamido penta acetic acid, diethyl triamine base penta acetic acid, N-(2-ethoxy)-ethylenediamine triacetic acid trisodium salt, in N-two (2-ethoxy) glycine one or more; Preferred L-cysteine hydrochloride, sodium sulfite, EDTA disodium, sodium pyrosulfite.Antioxidant or stabilizing agent addition (weight ratio) are the 0.0001-5% of total amount, preferred 0.001-1%.
Compound diisopropylamine dichloroacetate freeze-dried powder preparation method is:
A. under cleaning condition, get the diisopropylamine dichloroacetate of recipe quantity and gluconic acid sodium salt in an amount of water for injection, stirring and dissolving; Get it filled and use adjuvant: excipient, antioxidant, stabilizing agent, in an amount of water for injection, stirring and dissolving;
B. add 0.005%～5% needle-use activated carbon by amount of preparation, preferred 0.05%～0.5%, stir 10-120min, preferred 15-30min, 5-30 μ m filter filtering decarbonization, add the injection water, stir evenly, regulate pH value, work as after the assay was approved with the pH regulator agent, with 0.45-0.8um filtering with microporous membrane, the degerming of reuse 0.22～0.2um filtering with microporous membrane, fill according to dosage; Or 5-30 μ m filter stick or plate-and-frame filtration, two times of ultrafiltration degerming, the source of reducing phlegm and internal heat, according to dosage fill;
C. the bottle that branch is installed places freeze dryer, and precooling 0.5-9 hour, be preferably 1-4 hour, make temperature reach-15～-70 ℃, preferred-20～-50 ℃.Making the interior vacuum of machine is 0.01-200Pa, is preferably 1-50Pa, makes temperature reach-15～-70 ℃, low-temperature vacuum drying 10-60 hour, temperature risen to be not higher than 60 ℃, vacuum drying 1-24 hour, be preferably 3-10 hour, the unit dose that makes diisopropylamine dichloroacetate is 20～100mg, be preferably 20～60mg, the unit dose of gluconic acid sodium salt is 19～100mg, is preferably 19～57mg, control its pH value between 2～7.5, jump a queue, gland promptly.
In the hyperfiltration process, that ultrafilter can be selected for use is flat, rolling, tubular type, doughnut formula and circle boxlike etc., preferred rolling and doughnut formula ultrafilter, it is after 50,000 to 300,000 filter membrane is removed most of heat generation material and antibacterial that relative molecular mass is held back in employing, adopt the ultrafilter membrane of holding back relative molecular mass 1000-30000 to remove the residue thermal source, the ultrafilter membrane of preferred relative molecular mass 1000-10000 again.
The percentage by weight of moisture content is between 0.01-8% in the control preparation, and preferred 0.01-3% controls its pH value between 2～7, and preferred pH value is beneficial to the stable of said preparation between 4.5～7.
Although General Purpose Rubber, ampoule bottle all can be packaging material, the preferred butyl rubber of freeze-dried powder of the present invention, chlorinated scoline, brombutyl plug, cillin bottle are formed the compound diisopropylamine dichloroacetate freeze-dried powder as packaging material.
Compound diisopropylamine dichloroacetate freeze-dried powder of the present invention, through 6 months accelerated stability The effects, its character, clarity, related substance, pyrogen, content all met the requirements.With embodiment 3 compound diisopropylamine dichloroacetate freeze-dried powders, 80 ℃ high temperature experiment through 10 days, its character, clarity, related substance, pyrogen, content all meet the requirements, but compound diisopropylamine dichloroacetate liquid drugs injection (national drug standards WS-10001-(HD-1339)-2003) was through 10 days high temperature experiment, check that with GLC catabolite obviously increases.
It is on the low side that the present invention changes the unit dose of principal agent of compound diisopropylamine dichloroacetate liquid drugs injection, has only 20mg/1ml, 40mg/2ml specification, and pharmaceutical preparation goes up the irrational phenomenon of design.Therefore, this not only reduces the doubly above packaging material of 1-2 and the waste of human resources, helps to raise labour productivity.And the present invention also overcomes the deficiency of compound diisopropylamine dichloroacetate liquid drugs injection, improve stability of drug, help medicament transport and preservation, avoid liquid drugs injection easily to freeze simultaneously in winter, influence the quality of medicine, the storage life of prolong drug, improve the quality of medicine, so that it is safer, more effectively be used for hepatic insufficiency that acute and chronic hepatitis, fatty liver, early stage liver cirrhosis, other diseases causes, be used for peripheral terminals and cerebral blood vessel imbalance, improve apoplexy sequela, the auxiliary treatment of diseases such as hypertension.
Usage and dosage: generally, for the adult, intramuscular injection, intravenous injection or the 20-60mg that instils a time, once-a-day, in particular cases, dosage is multiplicable, face with before, with the quiet notes in 25% glucose injection 20ml dilution back, also available 5% glucose injection 250-500ml dilution back instillation.Child more than 8 years old reduces by half.
The specific embodiment
Mode by the following examples further specifies the present invention, but does not limit the present invention in any way.
Embodiment 1: under cleaning condition, get diisopropylamine dichloroacetate 20g, gluconic acid sodium salt 19g, arginase 12 00g respectively, 2-hydroxypropyl 10g, sodium sulfite 0.5g in 20 ℃ of an amount of waters for injection, stirring and dissolving; Regulate pH value with dilute hydrochloric acid, add the 1g needle-use activated carbon, stir 20min, 10 μ m titanium material filter stick filtering decarbonizations, pH value and after the assay was approved are with 0.45-0.8um filtering with microporous membrane, reuse 0.2-0.22um filtering with microporous membrane; Degerming, the source of reducing phlegm and internal heat, according to dosage be sub-packed in the cillin bottle, making diisopropylamine dichloroacetate unit dose in every bottle is that the unit dose of 20mg, gluconic acid sodium salt is 19mg, add plug, the bottle that branch is installed, place freeze dryer, freezing 2 hours, make temperature reach-45 ℃, making the interior vacuum of machine is 10Pa, low-temperature vacuum drying 18 hours, temperature is raised to 35 ℃, vacuum drying 9 hours, inflated with nitrogen, jump a queue, gland promptly, the percentage by weight of controlling its moisture content is at 0.05-3%, and its pH value is between 4.5～6.
Embodiment 2: under cleaning condition, get diisopropylamine dichloroacetate 40g, gluconic acid sodium salt 38g, sodium chloride 10g, lysine 10g respectively, 2-hydroxypropyl 5g, nicotiamide 20g, L-cysteine hydrochloride 0.1g in 20 ℃ of an amount of waters for injection, stirring and dissolving; Regulate pH with glucuronic acid and sodium hydroxide, 5 μ m titanium material filter sticks filter, add the injection water, treat pH value and after the assay was approved, the two times of ultrafiltration degerming, the source of reducing phlegm and internal heat, according to dosage be sub-packed in the cillin bottle, the unit dose that makes diisopropylamine dichloroacetate in every bottle is 40mg, the unit dose of gluconic acid sodium salt is 38mg, adds plug, the bottle that branch is installed, place freeze dryer, freezing 2 hours, make temperature reach-50 ℃, making the interior vacuum of machine is 10Pa, low-temperature vacuum drying 30 hours, temperature is risen to 30 ℃, vacuum drying 10 hours, inflated with nitrogen, jump a queue, gland promptly, the percentage by weight of controlling its moisture content is at 0.05-3%, and its pH value is between 4.5～6.
Embodiment 3: under cleaning condition, get diisopropylamine dichloroacetate 60g, gluconic acid sodium salt 57g, glucose 1000g, arginine 100g respectively, 3-hydroxypropyl 20g, sodium pantothenate 50g, sodium pyrosulfite 2g in 20 ℃ of an amount of waters for injection, stirring and dissolving; Regulate pH with hydrochloric acid and sodium hydroxide, 10 μ m titanium material filter sticks filter, and add the injection water, stir evenly, pH value and after the assay was approved, the two times of ultrafiltration degerming, the source of reducing phlegm and internal heat according to dosage is sub-packed in the cillin bottle, the unit dose that makes diisopropylamine dichloroacetate in every bottle is 60mg, the unit dose of gluconic acid sodium salt is 57mg, adds plug, the bottle that branch is installed, place freeze dryer, freezing 2 hours, make temperature reach-40 ℃, making the interior vacuum of machine is 10Pa, low-temperature vacuum drying 30 hours, temperature is risen to 30 ℃, vacuum drying 10 hours, the percentage by weight of controlling its moisture content is at 0.05-3%, its pH value between 4.5～6, inflated with nitrogen, jump a queue, gland promptly.
Embodiment 4: under cleaning condition, get diisopropylamine dichloroacetate 60g, gluconic acid sodium salt 57g, lysine 100g, glucose 1500g, 2-hydroxypropyl 20g, EDTA disodium 0.5g respectively in 20 ℃ of an amount of waters for injection, stirring and dissolving; Regulate pH with citric acid and sodium hydroxide, stirring and dissolving adds the 10g needle-use activated carbon by amount of preparation, stir 20min, 10 μ m titanium material filter sticks filter, pH value and after the assay was approved, two times of ultrafiltration degerming, the source of reducing phlegm and internal heat, according to dosage be sub-packed in the cillin bottle, making the unit dose of diisopropylamine dichloroacetate in every bottle is 60mg, adds plug, the bottle that branch is installed, place freeze dryer, freezing 8 hours, make temperature reach-60 ℃, making the interior vacuum of machine is 5Pa, low-temperature vacuum drying 30 hours, temperature is risen to 35 ℃, vacuum drying 16 hours, the percentage by weight of controlling its moisture content is at 0.08-3%, its pH value between 5～6, inflated with nitrogen, jump a queue, gland promptly.
Embodiment 5: under cleaning condition, get diisopropylamine dichloroacetate 40g, gluconic acid sodium salt 38g, L-cysteine hydrochloride 0.1g respectively in 20 ℃ of an amount of waters for injection, stirring and dissolving; Regulate pH with sodium hydroxide, 10 μ m titanium material filter sticks filter, and add the injection water, stir evenly, pH value and after the assay was approved, the two times of ultrafiltration degerming, the source of reducing phlegm and internal heat according to dosage is sub-packed in the cillin bottle, and the unit dose that makes diisopropylamine dichloroacetate in every bottle is 40mg, add plug, bottle with branch installs places freeze dryer, freezing 2 hours, make temperature reach-40 ℃, making the interior vacuum of machine is 10Pa, and low-temperature vacuum drying 20 hours rises to 20 ℃ with temperature, vacuum drying 10 hours, the percentage by weight of controlling its moisture content is at 0.05-3%, and its pH value is jumped a queue between 5～6, gland promptly.
The variation that is appreciated that a lot of details is possible, and therefore this do not limit the scope of the invention and spirit.
Claims (10)
1, a kind of compound diisopropylamine dichloroacetate freeze-dried powder, it is characterized in that: the diisopropylamine dichloroacetate 10-200mg that wherein contains unit dose, gluconic acid sodium salt 9.5-200mg, and containing a kind of pharmaceutically acceptable carrier at least, carrier comprises: excipient, pH regulator agent, antioxidant, stabilizing agent; And in container, to provide with unit dosage form.
2, compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1 is characterized in that: excipient is a dextran, mannitol, glucose, sorbitol, sucrose, lactose, lactose monohydrate, lactose, trehalose, maltose, xylose, xylitol, glucide, gluconic acid and salt, glucuronic acid and salt, magnesium chloride, sodium chloride, sodium sulfate, succinic acid and salt thereof, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium lactobionate., polyvinylpyrrolidone, cetomacrogol 1000-4000, magnesium sulfate, inositol, phytic acid, imidazoles, nicotiamide, citric acid, citrate, pantothenic acid and salt thereof, agedoite, aminoacid and amino acid salts, cholate, glycyrrhizic acid, glycyrrhetate, enoxolone, glycyrrhetate, water for injection, gelatin hydrolysate, soluble starch, soluble cellulose class material, cyclodextrin or cyclodextrin derivative.
3, cyclodextrin according to claim 2 or cyclodextrin derivative is characterized in that: cyclodextrin or cyclodextrin derivative comprise alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, glucityl-cyclodextrin (G
1-CYD), comprise glucosyl group-alpha-cyclodextrin (G
1-α-CYD), glucose group-beta-cyclodextrin (G
1-β-CYD), didextrose group-beta-cyclodextrin (2G
1-β-CYD), malt-base-cyclodextrin (G
2-CYD), malt-base-alpha-cyclodextrin (G
2-α-CYD), malt sugar group-beta-cyclodextrin (G
2-β-CYD), malt-base-gamma-cyclodextrin (G
2-γ-CYD), maltotriose glycosyl-cyclodextrin (G
3-CYD), maltotriose glycosyl-alpha-cyclodextrin (G
3-α-CYD), G 3-(G
3-β-CYD), maltotriose glycosyl-gamma-cyclodextrin (G
3-γ-CYD), methyl beta-schardinger dextrin-, ethyl beta-schardinger dextrin-, dimethyl-, 2,6 dimethyl-s (DM-β-CYD), 2,3,6 trimethyl beta-schardinger dextrin-s (TM-β-CYD), beta-schardinger dextrin-sulfoalkyl ether (SAE-β-CYD), ethoxy beta-schardinger dextrin-, hydroxypropyl, 2-hydroxypropyl (2-HP-β-CYD), 3-hydroxypropyl (3-HP-β-CYD), 2,3-dihydroxypropyl beta-schardinger dextrin-(DHP-β-CYD), cyclodextrin CDPS, CDPS-H, CDPS-L.
4, the excipient of compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1 and 2 is characterized in that: excipient is glucose, mannitol, sorbitol, lysine, arginine, sodium chloride, nicotiamide, sodium pantothenate, 2-hydroxypropyl, water for injection.
5, compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1, it is characterized in that: the PH regulator is a hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, hydrobromic acid, formic acid, propanoic acid, acetic acid and acetate, potassium acetate, sodium acetate, ammonium acetate, boric acid, lactic acid, the lactic acid pharmaceutical salts, sodium lactate, citric acid, citrate, disodium citrate, the citric acid trisodium, sodium citrate, citric acid monohydrate, potassium citrate, natrium carbonicum calcinatum, sal soda, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, soda-lime, calcium oxide, water for injection, phosphate, dalcium biphosphate, calcium hydrogen phosphate, calcium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, diammonium phosphate, dipotassium hydrogen phosphate, maleic acid, succinic acid and salt, phytic acid, D-tartaric acid, L (+)-tartaric acid, tartrate, sodium bitartrate, DL-tartaric acid, potassium hydrogen tartrate, sodium potassium tartrate tetrahydrate, Borax, boric acid, succinic acid, caproic acid, adipic acid, fumaric acid, ammonium carbonate, drikold, liquid CO 2, the aromatic amine fine wine, hypophosphorous acid, Polymeric sodium metaphosphate., Kurrol's salt, potassium metaphosphate, Tris, triethanolamine, diethanolamine, ethanolamine, isopropanolamine, diisopropanolamine (DIPA), 2-amino-2-(methylol) 1, ammediol amine, 1, the 2-hexamethylene diamine, N-methyl Fructus Vitis viniferae amine, diisopropylamine and their salt, multi-hydroxy carboxy acid and salt, glucuronic acid, gluconic acid, lactobionic acid, lactobionic acid, galacturonic acid, malic acid, threonic acid THREONIC ACID., glucoheptonic acid, two (hydroxymethyl) acetic acid, trihydroxy-butyric acid, hydroxyacetic acid, dihydroxy-acid, the dihydroxy butanoic acid, the dihydroxy isovaleric acid, the dihydroxy isopropylformic acid., 2,3-dihydroxy 1,3-propanedicarboxylic acid, the dihydroxy adipic acid, nicotinic acid, concentrated ammonia solution, dilute ammonia solution, carbon dioxide, δ-gluconic acid lactone, phytic acid (phytic acid) and salt, benzoic acid and salt, sodium benzoate, methanesulfonic acid, benzenesulfonic acid, p-methyl benzenesulfonic acid, glyceric acid, glycine, lysine, arginine, methionine, aminoacid and amino acid salts.
6, compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1, it is characterized in that: its antioxidant and stabilizing agent are sulfurous acid, sulphite, bisulfites, pyrosulfite, dithionite, thiosulfate, the organosulfur compound thiourea, glutathion, dimercaptopropanol, BAL, TGA and salt, sodium sulfoxylate formaldehyde, thioglycerin, 2-mercaptopropionic acid and salt, thio-2 acid and salt, the sulfo-sorbitol, thiosalicylic acid, dithiooxamide, oxine, pyridoxamine and salt, phenol compound, as gallic acid and salt, progallin A, propyl gallate, gallateoctylester, lauryl gallate, caffeic acid, the caffeiate, ferulic acid, ferulate, dibenzylatiooluene, butylated hydroxyarisol, the di-t-butyl Pyrogentisinic Acid, nordihydroguaiaretic acid (NDGA), 2, the 5-resorcylic acid, 2,5-resorcylic acid salt, phytic acid and salt, the phenol or derivatives thereof, salicylic acid or its salt; Sodium glutamate, glycine, cysteine, methionine, L-leucine, L-isoleucine, L-tryptophan, L-lysine, L-methionine, L-a word used in person's names propylhomoserin, aminoacid with and salt; Glycyrrhetate, glycyrrhetate, enols used, as ascorbic acid and Ascorbate, ascorbic acid Petiolus Trachycarpi ester, arabo-ascorbic acid and erythorbate, acetone closes ascorbic acid, the a-tocopherol, the L-cysteine, the L-cysteine hydrochloride, nicotiamide, tartaric acid, nitrate, phosphate, the acetic acid pharmaceutical salts, citrate, EDTA and EDTA one sodium, the EDTA disodium, EDTA four sodium, calcium disodium edetate, divinyl triamido penta acetic acid, diethyl triamine base penta acetic acid, N-(2-ethoxy)-ethylenediamine triacetic acid trisodium salt, N-two (2-ethoxy) glycine.
7, compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1, it is characterized in that: the percentage by weight of its moisture content is at 0.01-8%.
8, compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1, it is characterized in that: the percentage by weight of its moisture content is at 0.01-3%.
9, compound diisopropylamine dichloroacetate freeze-dried powder according to claim 1, it is characterized in that: its pH value is between 2～7.
10, a kind of compound diisopropylamine dichloroacetate freeze-dried powder preparation method is characterized in that freeze-drying process is:
A. under cleaning condition, get the diisopropylamine dichloroacetate of recipe quantity and gluconic acid sodium salt in an amount of water for injection, stirring and dissolving; Get it filled and use adjuvant: excipient, antioxidant, stabilizing agent, in an amount of water for injection, stirring and dissolving;
B. add 0.005%～5% needle-use activated carbon by amount of preparation, stir 10～120min, 5-30 μ m filter filtering decarbonization, add the injection water, stir evenly, regulate pH value, work as after the assay was approved with the pH regulator agent, with 0.45～0.8um filtering with microporous membrane, reuse 0.2um～0.22um filtering with microporous membrane degerming, fill according to dosage; Or filter two times of ultrafiltration degerming again, the source of reducing phlegm and internal heat, according to dosage fill with aperture 5～30 μ m filters;
C. the bottle that branch is installed, place freeze dryer, precooling 0.5～9 hour, make temperature reach-15～-70 ℃, making the interior vacuum of machine is 0.01～200Pa, low-temperature vacuum drying 10-60 hour, temperature risen to be not higher than 60 ℃, vacuum drying 1-24 hour, control its pH value between 2～7, inflated with nitrogen or argon, jump a queue, gland promptly.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200310111617 CN1628650A (en) | 2003-12-19 | 2003-12-19 | Compound diisopropylamine dichloroacetate freeze dried injection and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213120A (en) * | 2017-06-09 | 2017-09-29 | 安徽赛诺制药有限公司 | A kind of Diisopropylamine Dichloroacetate freeze-dried powder and preparation method thereof |
| CN110177771A (en) * | 2016-09-06 | 2019-08-27 | 代谢科技有限公司 | For treating, preventing or improving the composition and application method of the γ -one aldehyde scavenger of non-alcoholic fatty liver disease (NAFLD), NASH, ALD or liver related pathologies |
-
2003
- 2003-12-19 CN CN 200310111617 patent/CN1628650A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110177771A (en) * | 2016-09-06 | 2019-08-27 | 代谢科技有限公司 | For treating, preventing or improving the composition and application method of the γ -one aldehyde scavenger of non-alcoholic fatty liver disease (NAFLD), NASH, ALD or liver related pathologies |
| CN110177771B (en) * | 2016-09-06 | 2022-12-13 | 代谢科技有限公司 | Compositions and methods of use of gamma-ketoaldehyde scavengers for treating, preventing or ameliorating nonalcoholic fatty liver disease (NAFLD), NASH, ALD, or liver-related conditions |
| CN107213120A (en) * | 2017-06-09 | 2017-09-29 | 安徽赛诺制药有限公司 | A kind of Diisopropylamine Dichloroacetate freeze-dried powder and preparation method thereof |
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