CN112438949A - Tomoxxetine hydrochloride oral liquid containing calcium supplement and preparation method thereof - Google Patents
Tomoxxetine hydrochloride oral liquid containing calcium supplement and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
Abstract
The invention discloses a pharmaceutical composition of tomoxetine hydrochloride containing a calcium supplement, which is sour, sweet and delicious in taste and comprises tomoxetine hydrochloride, a preservative, a pH regulator, a corrigent, a calcium supplement and an essence. The invention overcomes the heavy bitter taste of the tomoxetine hydrochloride, has good administration compliance, can effectively relieve the pain of patients, improves the treatment efficiency and is beneficial to the patients to supplement calcium ions, and the calcium deficiency is a direct cause of the children's attention deficit hyperactivity disorder, so the invention provides the tomoxetine hydrochloride oral liquid with the calcium supplement effect, which has milestone significance for treating the children's attention deficit hyperactivity disorder and simultaneously reduces the growth retardation of the patients caused by side effects in the long-term administration process of the tomoxetine hydrochloride.
Description
Technical Field
The invention particularly relates to a tomoxetine hydrochloride oral liquid containing a calcium supplement for treating Attention Deficit Hyperactivity Disorder (ADHD) of children and teenagers and a preparation method thereof, belonging to the technical field of medicines and preparation methods thereof.
Background
Tomoxetine hydrochloride (atomoxetine hydrochloride), chemical name: (R) -N-methyl-3- (2-tolyloxy) -3-phenyl-1-propylamine hydrochloride.
Tomoxetine hydrochloride was developed by american etiquette pharmaceutical company and marketed in the united states in 1 month 2003 under the trade name selectada (Strattera) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents in the form of capsules of six specifications 5mg, 10mg, 18mg, 25mg, 40mg and 60 mg. It has been marketed and applied in several countries such as the United states, Australia, Canada, UK, China, 11 months in 2013, and the Ling company introduced oral solution formulations in Japan (Strattera)®0.4%). Tomoxetine hydrochloride is a selective inhibitor of presynaptic norepinephrine transporter, it can prolong the activity of norepinephrine released in synaptic clefts, and it has great market prospects as the first large number of experiments to confirm that effective therapeutic stimulants specific for ADHD have been shown.
At present, the Chinese medicine is mainly used for treating Attention Deficit Hyperactivity Disorder (ADHD) diseases, one medicine is a central stimulant, the other medicine is a selective norepinephrine reuptake inhibitor, and the tomoxetine hydrochloride is a representative medicine of the selective norepinephrine reuptake inhibitor, and has the advantages of small side effect, good tolerance, no addiction after long-term use and the like. The tomoxetine hydrochloride has low onset of action and can be taken every day, so the tomoxetine hydrochloride is a better safe and effective medicine for treating ADHD diseases.
The 25 th national research conference of pediatrics science and medicine and the scientific research treatise on the education of high grade of traditional Chinese medicine and pediatrics, which is specifically written in the relation review of trace elements and attention deficit hyperactivity disorder of children, clearly shows that the direct attention of children is influenced by calcium deficiency, so the calcium deficiency is a direct cause of the attention deficit hyperactivity disorder of children. Therefore, the addition of the calcium supplement has a drug therapy synergistic effect on the tomoxetine hydrochloride oral liquid.
The main side effects of the tomoxetine hydrochloride are aggression, irritability, lethargy and vomiting, constipation, dry mouth, abdominal distension, nausea, dizziness, headache, insomnia, dreaminess and the like, most parents worry about the growth retardation of children and teenagers due to the side effect of the medicament in the long-term taking of the tomoxetine hydrochloride oral liquid, and the calcium gluconate is the most extensive calcium supplement for preventing and treating calcium deficiency of the children, can maintain the normal excitability of nerve and muscle, has a certain sedative effect, can improve the symptoms of osteoporosis, tetany, bone hypoplasia, rickets and the like of the children and the teenagers, and therefore, the calcium gluconate has a certain calcium supplementing effect on the patients to improve the growth retardation phenomenon due to the side effect of the medicament. The study is carried out aiming at the dosage of the calcium gluconate and the stability of the added tomoxetine hydrochloride oral liquid.
For preventing to lead to the product to appear in the stable process of placing of later stage after adding calcium gluconate in tomoxetine hydrochloride oral liquid and appearing precipitating the problem, this patent adopts to add citric acid and/or sodium citrate with solution pH value control between 3.7 ~ 4.3, adds erythritol, sucralose and propylene glycol in the solution simultaneously and has improved the viscosity of solution, has reduced the formation of calcium gluconate crystal nucleus, has reduced the risk that calcium gluconate crystallization in the oral liquid is appeared.
Tomoxetine hydrochloride is a highly water-soluble drug with a strong bitter taste, a property that seriously affects compliance during administration of the drug. According to research and investigation, part of parents can mix the medicine with children's diet to increase administration compliance, and the measure can influence the curative effect of the medicine, so that the development of the tomoxetine hydrochloride oral liquid with good taste is an important strategy for improving the administration compliance of patients by masking or reducing the bitter taste of the medicine through a preparation method.
The erythritol can be used as a flavoring agent of the medicine, and can effectively improve the taste of the medicine. Erythritol is a natural substance widely present in fungi (such as seaweed, shiitake mushroom, etc.), fruits (melon, grape, etc.) and various fermented foods (such as vinasse, sweetgum, sake, soy sauce, etc.), and erythritol components are also present in human or animal tissues and body fluids, such as blood, semen, urine. Because of the characteristics of low calorie and no influence on blood sugar level, the red fresh sugar alcohol is particularly suitable for replacing cane sugar to prepare a health care product with low calorie value, and meets the special requirements of diabetes patients, obesity patients, hypertension patients and cardiovascular patients on the sweetener. Erythritol also has a significant effect in proliferating bifidobacteria and in combating dental caries.
Disclosure of Invention
The invention provides a tomoxetine hydrochloride oral liquid containing a calcium supplement and a preparation process of the oral liquid.
The present invention provides a pharmaceutical composition comprising an oral solution of tomoxetine hydrochloride, a preservative, a flavoring agent, a calcium supplement, a pH adjusting agent, a flavor, and water.
The invention provides a tomoxetine hydrochloride medicinal composition with the pH value of 3.0-5.0.
The invention provides a pharmaceutical composition which comprises tomoxetine hydrochloride, a preservative which is one or more of sodium benzoate, methylparaben, ethylparaben and propylparaben, a flavoring agent which is one or more of erythritol, sorbitol, xylitol, maltitol, mannitol, sucralose, glycerol and propylene glycol, a calcium supplement which is calcium gluconate, a pH regulator which is one or more of disodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, sodium dihydrogen phosphate monohydrate, phosphoric acid, citric acid and sodium citrate, and an essence which is one or more of grapefruit, banana, lime and pineapple essences.
The invention provides a pharmaceutical composition which comprises tomoxetine hydrochloride, sodium benzoate as a preservative, erythritol, sucralose and propylene glycol as a corrigent, citric acid and/or sodium citrate as a pH regulator, calcium gluconate as a calcium supplement and one or more of grapefruit, banana, lime and pineapple essences as an essence.
The invention provides a pharmaceutical composition of an oral solution, wherein the preferred concentration of the oral solution is 4.0-5.0 mg/ml of tomoxetine hydrochloride, 0.5-1.0 mg/ml of sodium benzoate, 280-320 mg/ml of erythritol, 5-50 mg/ml of sucralose, 5-50 mg/ml of calcium gluconate, 20-60 mg/ml of propylene glycol and 1-3 mg/ml of essence, and the preferred pH value of the solution is 3.7-4.3.
The invention provides a pharmaceutical composition of an oral solution comprising tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol and an essence, wherein the more preferable concentration of the tomoxetine hydrochloride solution is 4.6 mg/ml.
The invention provides a pharmaceutical composition of an oral solution comprising tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol, and an essence, wherein the more preferable concentration of sodium benzoate is 0.8 mg/ml.
The invention provides a pharmaceutical composition of an oral solution comprising tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol and an essence, wherein the more preferable concentration of erythritol is 300 mg/ml.
The invention provides a pharmaceutical composition of an oral solution containing tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol and essence, wherein the more preferable concentration of the sucralose is 10 mg/ml.
The invention provides a pharmaceutical composition of an oral solution containing tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol and essence, wherein the more preferable concentration of the calcium gluconate is 10 mg/ml.
The invention provides a pharmaceutical composition of an oral solution comprising tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol and an essence, wherein the more preferable concentration of the propylene glycol is 50 mg/ml.
The invention provides a pharmaceutical composition of an oral solution comprising tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol, and an essence, wherein the more preferred concentration of the essence is 1 mg/ml.
The invention provides a pharmaceutical composition of an oral solution containing tomoxetine hydrochloride, sodium benzoate, erythritol, sucralose, citric acid and/or sodium citrate, calcium gluconate, propylene glycol and essence, wherein the pH value of the solution is adjusted to 3.7-4.3 by adopting citric acid and/or sodium citrate, and the pH value is more preferably 4.0.
The invention also provides a preparation method of the tomoxetine hydrochloride oral solution, which comprises the following steps:
(1) adding the preservative into purified water, and stirring until the preservative is completely dissolved;
(2) adding a flavoring agent and a taste masking agent into the solution 1, and stirring until the flavoring agent and the taste masking agent are completely dissolved;
(3) adding tomoxetine hydrochloride into the solution 2, and stirring until the tomoxetine hydrochloride is completely dissolved;
(4) adding essence into the solution 3, and stirring until the essence is completely dissolved;
(5) adjusting the pH value of the solution to 3.7-4.3 by using citric acid and/or sodium citrate;
(6) purified water was added to solution 5 to achieve a concentration of 4.6mg/ml tomoxetine hydrochloride;
(7) filtering with 0.22 μm polypropylene (PP) filter membrane to remove physical impurities and ensure the clarity to be qualified.
The pharmaceutical composition of tomoxetine hydrochloride successfully reduces the bitter taste of tomoxetine hydrochloride, and the taste presents a sweet and sour delicious taste.
The invention is further illustrated by the following examples. It should be understood that: the embodiments of the present invention are given for illustration only, and not for limitation, and the simple modifications of the present invention based on the technical solutions of the present invention belong to the protection scope of the present invention.
Examples 1 to 3
TABLE 1 composition, concentration and function of oral tomoxetine hydrochloride solution
Adding 500g of purified water into a container, adding 0.8g of sodium benzoate, stirring until the sodium benzoate is completely dissolved, adding 300g of erythritol into the solution, continuously stirring until the solid is completely dissolved, adding 10g of sucralose, stirring until the sucralose is completely dissolved, adding 10g of calcium gluconate in example 1, stirring until the calcium gluconate is completely dissolved, adding 50g of propylene glycol in example 2, adding 5g of calcium gluconate in example 2, stirring until the calcium gluconate is completely dissolved, adding 50g of propylene glycol in example 3, adding 10g of calcium gluconate, stirring until the calcium gluconate is completely dissolved, adding 30g of propylene glycol, adding 4.6g of tomoxetine hydrochloride after the materials are completely dissolved, stirring until the calcium gluconate and/or sodium citrate are completely dissolved, adjusting the pH value of the solution to 4.0 by using citric acid and/or sodium citrate, and adding purified water to fix the volume to 1L. The solution was filtered through a 0.22 μm polypropylene aqueous filter.
Taste testing
10 subjects were selected and taste tests were randomly performed on the tomoxetine hydrochloride oral solution obtained in examples 1 to 3, and the test results were rated according to the following table rating scale. The taste evaluation ratings of 10 subjects for each tomoxetine hydrochloride oral solution, with one highest score and one lowest score removed, were calculated on average and the evaluation results are given in the following table:
TABLE 2 taste ratings
TABLE 3 taste evaluation Table for tomoxetine hydrochloride oral solutions (examples 1-3)
The results of the examples 1-3 in table 3 show that the strong bitter taste of tomoxetine hydrochloride can be masked by adding erythritol, calcium gluconate and propylene glycol, and after the amounts and the proportions of calcium gluconate and propylene glycol are screened, it is determined that the taste effect of the example 1 is the best, and the flavor is screened in the later stage.
Example 4
Tomoxxetine hydrochloride oral solution with grapefruit taste
A solution of tomoxetine hydrochloride of the present invention was prepared as prepared in example 1, with the addition of 0.1% grapefruit essence.
Example 5
Tomoxxetine hydrochloride oral solution with banana taste
A solution of tomoxetine hydrochloride of the present invention was prepared as prepared in example 1, with the addition of 0.1% banana essence.
Example 6
Tomoxetine hydrochloride oral solution with lime taste
A solution of tomoxetine hydrochloride according to the present invention was prepared as prepared in example 1, with the addition of 0.1% lime flavor.
Example 7
Tomoxetine hydrochloride oral solution with pineapple taste
A solution of tomoxetine hydrochloride of the present invention was prepared as prepared in example 1, with the addition of 0.1% pineapple essence.
Taste testing
10 subjects were selected and taste test was randomly performed on the tomoxetine hydrochloride oral solution obtained in examples 4 to 7, and the test results were evaluated according to 00030 rating scale. The results are as follows:
TABLE 4 taste evaluation Table for tomoxetine hydrochloride oral solutions (examples 4 to 7)
TABLE 5 stability evaluation Table for tomoxetine hydrochloride oral solutions (examples 4 to 7)
Compared with the unflavored example 1, the flavors with different tastes in examples 4-7 can make the tomoxetine hydrochloride show a more attractive fruit taste and reduce the bitterness, and after the taste screening of 10 subjects, the tomoxetine hydrochloride oral liquid with the pineapple taste in example 7 has the best taste effect.
The separation phenomenon is observed by the experiment of placing the pharmaceutical composition at normal temperature and low temperature for 3 months, and the pharmaceutical composition of tomoxetine hydrochloride with the calcium supplementing effect, which is prepared by the preparation method disclosed by the patent, has better stability.
According to the formula, the taste is heavier in entrance sweetness and slightly bitter after aftertaste, the viscosity of a solution is improved by adding erythritol, sucralose and propylene glycol as flavoring agents, the risk of calcium gluconate crystal calcium precipitation is reduced, the pH value of the solution is controlled to be 3.7-4.3 by selecting citric acid and sodium citrate as pH regulators, and the taste is adjusted by pineapple essence, so that the tomoxetine hydrochloride presents sweet and sour taste.
Claims (10)
1. A tomoxetine hydrochloride oral liquid containing a calcium supplement comprising: the oral liquid comprises tomoxetine hydrochloride, a preservative, a pH regulator, a flavoring agent, a calcium supplement and essence, wherein the pH value of the oral liquid containing the calcium supplement and the tomoxetine hydrochloride is 3.0-5.0.
2. The tomoxetine hydrochloride oral liquid for a calcium supplement according to claim 1, comprising one or more preservatives selected from sodium benzoate, methylparaben, ethylparaben and propylparaben, one or more corrigents selected from erythritol, sorbitol, xylitol, maltitol, mannitol, sucralose, propylene glycol and glycerol, one or more pH regulators selected from disodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, sodium dihydrogen phosphate monohydrate, phosphoric acid, citric acid and sodium citrate, and one or more essences selected from grapefruit, banana, lime and pineapple essences.
3. The tomoxetine hydrochloride oral liquid for a calcium supplement according to claims 1 and 2, wherein: the preservative is sodium benzoate, the flavoring agent is erythritol, sucralose and propylene glycol, the pH regulator is citric acid and/or sodium citrate, the calcium supplement is calcium gluconate, and the essence is one or more of grapefruit, banana, lime and pineapple essences.
4. The tomoxetine hydrochloride oral liquid for the calcium supplement according to claims 1 to 3, wherein the concentration of the tomoxetine hydrochloride is preferably 4.0 to 5.0 mg/ml, the concentration of sodium benzoate is preferably 0.5 to 1.0 mg/ml, the concentration of erythritol is preferably 280 to 320 mg/ml, the concentration of sucralose is preferably 5 to 50 mg/ml, the concentration of calcium gluconate is preferably 5 mg/ml to 50 mg/ml, the concentration of propylene glycol is preferably 20 mg/ml to 60 mg/ml, the concentration of essence is 1 to 3 mg/ml, and the preferred pH value of the solution is 3.7 to 4.3.
5. The tomoxetine hydrochloride oral liquid for the calcium supplement according to claim 1-3, wherein the concentration of tomoxetine hydrochloride is 4.6mg/ml and the concentration of sodium benzoate as a preservative is 0.8 mg/ml.
6. Use of a pharmaceutical composition according to any one of claims 1 to 5 for the preparation of a medicament for the treatment of attention deficit hyperactivity disorder and for calcium supplementation.
7. The method of claim 6, comprising the steps of:
(1) adding the preservative into purified water, and stirring until the preservative is completely dissolved;
(2) adding a flavoring agent and a taste masking agent into the solution 1, and stirring until the flavoring agent and the taste masking agent are completely dissolved;
(3) adding tomoxetine hydrochloride into the solution 2, and stirring until the tomoxetine hydrochloride is completely dissolved;
(4) adding essence into the solution 3, and stirring until the essence is completely dissolved;
(5) adjusting the pH of the solution to 3.7-4.3 by using a pH regulator;
(6) purified water was added to solution 5 to achieve a concentration of 4.6mg/ml tomoxetine hydrochloride;
(7) filtering with a filter membrane to remove physical impurities and ensure that the clarity of the solution is qualified.
8. The method for preparing tomoxetine hydrochloride oral liquid according to claim 7, wherein the preservative is sodium benzoate, the flavoring agent is erythritol, sucralose and propylene glycol, the pH regulator is citric acid and/or sodium citrate, the calcium supplement is calcium gluconate, and the essence is one or more of grapefruit, banana, lime and pineapple essences.
9. The method for preparing the tomoxetine hydrochloride oral liquid according to claim 7, wherein the concentration of the tomoxetine hydrochloride is 4.6mg/ml, the concentration of the preservative is 0.8 mg/ml, the concentration of erythritol is 300 mg/ml, the concentration of sucralose is 10 mg/ml, the concentration of calcium gluconate is 10 mg/ml, the concentration of propylene glycol is 50 mg/ml, the concentration of the essence is 1 mg/ml, and the pH value of the solution is adjusted to 3.7-4.3 by citric acid and/or sodium citrate.
10. Use of a pharmaceutical composition prepared by the process as claimed in any one of claims 7 to 9 for the treatment of attention deficit hyperactivity disorder and calcium supplementation.
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| CN201910838579.1A CN112438949A (en) | 2019-09-05 | 2019-09-05 | Tomoxxetine hydrochloride oral liquid containing calcium supplement and preparation method thereof |
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| CN201910838579.1A CN112438949A (en) | 2019-09-05 | 2019-09-05 | Tomoxxetine hydrochloride oral liquid containing calcium supplement and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015144255A1 (en) * | 2014-03-21 | 2015-10-01 | Lamda Laboratories S.A. | Oral solution comprising atomoxetine hydrochloride |
| CN105705135A (en) * | 2013-11-08 | 2016-06-22 | 伊莱利利公司 | Atomoxetine solution |
| CN107802608A (en) * | 2017-12-20 | 2018-03-16 | 威海贯标信息科技有限公司 | A kind of atomoxetine tablet composition |
| CN108785248A (en) * | 2018-09-20 | 2018-11-13 | 烟台巨先药业有限公司 | A kind of tomoxetine hydrochloride oral solution and preparation method thereof |
-
2019
- 2019-09-05 CN CN201910838579.1A patent/CN112438949A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105705135A (en) * | 2013-11-08 | 2016-06-22 | 伊莱利利公司 | Atomoxetine solution |
| WO2015144255A1 (en) * | 2014-03-21 | 2015-10-01 | Lamda Laboratories S.A. | Oral solution comprising atomoxetine hydrochloride |
| CN107802608A (en) * | 2017-12-20 | 2018-03-16 | 威海贯标信息科技有限公司 | A kind of atomoxetine tablet composition |
| CN108785248A (en) * | 2018-09-20 | 2018-11-13 | 烟台巨先药业有限公司 | A kind of tomoxetine hydrochloride oral solution and preparation method thereof |
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| Title |
|---|
| 宋昀晏等: "微量元素与儿童注意力缺陷多动障碍的关系", 《吉林医药学院学报》 * |
| 黄健红等: "儿童注意缺陷多动障碍与微量元素的关系", 《实用医学杂志》 * |
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