Good medicine no longer tastes bitter, so that sick children can recover in sweetness

Microfilm tablet press

　　Microfilm: the diameter is between 1-3mm, the content is uniform and the quality is controllable.

　　Diameter comparison between microchip and ordinary microchip.

　　The "microchip" medicine specially designed for children is small in size and easy to swallow.

Orally disintegrating tablets freeze-dried orally disintegrating tablets

　　"Freeze-dried orally disintegrating tablets" will immediately disperse in the mouth to prevent spitting.

　　Adults all know the truth that "good medicine tastes bitter and is good for disease", but for children, bitter medicine is unwilling to take even if it has a curative effect. In the future, in children’s medication, the bitter taste of good medicine may become history.

　　The pills will be made into cute little bears or cute kittens. Bitter potion adds sweet and sour "flavoring agent", which has strawberry flavor and orange flavor, depending on which one the baby likes; Naughty children will spit out after eating pills. After changing to "freeze-dried orally disintegrating tablets", the pills will spread on the tongue and disappear, and they can’t find pills when they want to vomit … …

　　The National Children’s Medical Center and Beijing Children’s Hospital affiliated to Capital Medical University, as the lead units, joined forces with the R&D forces of more than 30 scientific research institutes, universities and enterprises across the country to start the research and development of drug varieties and key technologies for children, which is also the 2017 project of the "Thirteenth Five-Year Plan" national "major new drug creation" and will be closed at the end of next year.

　　Ni Xin, the project leader and president of Beijing Children’s Hospital, said that the related technology of this project involves more than 100 kinds of children’s medicines. In the future, good medicines will no longer be bitter, and children will no longer need parents and children to "fight with each other".

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　　Oral medicine is too bitter

　　By the end of next year, a technical platform for correcting and masking the taste of children’s drugs will be built.

　　"One thing touched me deeply." Wang Xiaoling, director of the project office and director of the pharmacy department of Beijing Children’s Hospital, said that a child in the hospital was ill and had to take a sugar-coated tablet for adults. Because the dosage of the child was small, the sugar-coated tablet could only be ground and then fed to the child. "Once the sugar-coated tablet is destroyed, the bitter taste in the medicine will go straight to the entrance." The child was particularly angry and said, Why do adults take sweet medicine, but give me such bitter medicine? How can you adults be so bad! "This sentence makes me particularly shocked. Why can’t we adults try to make our children’s medicine no longer bitter?"

　　The child can’t understand the helplessness behind grinding a sugar-coated tablet and taking it again. His idea is very simple, that is, he wants to take medicine that is not bitter. Wang Xiaoling said that as one of the top ten tasks of the project, China will build a technical platform for correcting and masking the taste of children’s drugs by the end of next year. The specific technical types of taste correction and taste masking for children include taste masking technology, chemical taste masking technology and physical taste masking technology. "Some medicines are naturally bitter." Like other tastes, bitterness is a feeling caused by the stimulation of liquid containing chemical substances. Bitter substances existing in food and medicine basically naturally exist alkaloids, glycosides, bitter peptide bile and other substances, and some nitrogen-containing organic substances can also have a bitter feeling.

　　"We have established a bitterness database." Wang Xiaoling said that in the future, when children’s drug manufacturers develop new drugs, they can query the database and consider avoiding these bitter ingredients. However, the first thing to consider in drug research and development is curative effect. If bitter chemicals cannot be avoided, it is necessary to consider improving the taste of children’s drugs through taste correction technology or taste masking technology. "Just like giving people a double eyelid, beautify it."

　　The technology of taste masking and taste correction seems to be relatively uncommon, but in simple terms, it can be understood as the illusion of baby’s taste buds by adding "condiments"; It is also possible to avoid direct contact between bitter drugs and taste buds by adding auxiliary materials, or to temporarily paralyze taste buds. Now many babies have taken medicines that are not bitter, such as peaches, strawberries, oranges, hawthorn, milk tea and brown sugar … … Wang Xiaoling said that before the end of next year, the research group will also build a taste evaluation system for children in China. "Now many taste masking and taste correction technologies are imported. We should choose a taste that is more suitable for children in China according to the tastes of children in China."

　　The taste of children’s medication is not just "not bitter". Wang Xiaoling said that the waterless swallowing granule technology currently under development adopts technological innovation and high-quality auxiliary materials, which can effectively cover up the bad smell of drugs, and at the same time, it does not need water to be taken. After entering the stomach, the drugs are quickly dissolved and released, giving full play to the curative effect, greatly improving the compliance of children with drugs, and parents are no longer worried about the headache of drug administration.

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　　Dose is broken by hand

　　Customize different dosage packages for babies with professional packaging equipment.

　　In the young children’s ward of Beijing Children’s Hospital, pharmacists also have an important job of grinding pills for children. Hydrochlorothiazide, a commonly used medicine in children’s wards, is used to treat mild and moderate edema and hypertension, and can improve the symptoms of bronchial dysplasia. In the children’s ward, this is a drug that challenges pharmacists: the commonly used hydrochlorothiazide tablets are 25 mg per tablet, but the dosage of children needs to be calculated according to their weight. Some children need to use one-third tablets, and some children need to use one-quarter tablets. The youngest child needs to use 0.5 mg at a time, which is only 1/50 of one tablet. "Ordinary scales can’t be used for weighing, and analytical scales with higher accuracy must be used."

　　In the ward of Beijing Children’s Hospital, there are many commonly used divided-dose drugs. Compound sulfamethoxazole tablets are used to treat enteritis, endocarditis, acute bronchitis and chronic bronchitis in children’s hospitals, and are likely to be used in the departments of gastroenterology, cardiovascular medicine, respiratory medicine, neurology and infectious diseases. 79.95% of the compound sulfamethoxazole tablets used in children’s hospitals need to be divided into doses. Among the 199 kinds of oral drugs available in Beijing Children’s Hospital, 85 kinds of drugs, such as oral liquid, granules, dispersible tablets, etc., and 34 kinds of drugs with different doses, are excluded, and a total of 80 kinds of drugs need to be prepared in different doses, including 63 kinds of tablets and 12 kinds of capsules, as well as dosage forms such as enteric-coated tablets and sustained-release tablets.

　　According to the drug classification of clinical medication instructions, most of these 80 drugs are used for anti-infective drugs, nervous system, cardiovascular system, digestive system and endocrine system. Infection and digestive diseases are very common in children, and many children will use these drugs. Cardiovascular, endocrine and nervous system drugs sometimes need long-term out-of-hospital drug treatment. If there is no suitable dosage form specification and parents need to divide the dosage themselves, how to ensure the accurate dosage of drugs? How to ensure the proper storage of divided dose drugs? How to deal with the remaining drugs after dispensing? Is it necessary to buy an analytical balance specially for children to distribute medicine at home?

　　In some developed countries, such as Japan, personalized drug delivery has begun, which means that hospitals can use special equipment to package drugs separately. In China’s "Quality Management Standard for Pharmaceutical Work in Medical Institutions", there is also a clear definition of individualized dispensing — — According to the needs of patients’ individualized medication, qualified medical institutions can provide temporary preparation of special dosage forms or doses, such as diluting liquid, grinding tablets and subcontracting, subpackaging capsules, preparing temporary mixtures, and preparing ointments.

　　This year, the topic of personalized medication for young children has been added. At present, the research group has purchased sub-packaging equipment. In the future, Beijing Children’s Hospital can customize drugs with special doses for babies. "The content of a bag may be 10 micrograms or 5 milligrams, which can be designed completely according to the doctor’s advice. Parents give their children medicine, and they don’t have to guess. "

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　　It is difficult to swallow medicine.

　　Develop special formula technology

　　Develop special drugs for children

　　The problem of children’s medication is a worldwide topic. "We often say that children are not miniature versions of adults." Ni Xin said that children should choose special drugs for children. The project led by Beijing Children’s Hospital is based on the differentiated needs of children’s medication, developing special drug delivery technologies, including straw delivery, oral instant, micro-tablets, etc., and developing children’s drugs through the establishment of key technologies with distinctive differentiation.

　　For example, Wang Xiaoling said that according to the characteristics of children, the research group is still developing "microchips", that is, the diameter of tablets is between 1 and 3 mm, "too big tablets for children to swallow." After being changed into small tablets, the diameter is reduced to facilitate swallowing, and more importantly, the content of active ingredients in the medicine is uniform and the quality is controllable. Now adults are using sustained-release tablets, and the drugs can be released slowly. Adults can take the drugs once or twice a day. Children have to go to kindergarten and primary school, but many children need to take drugs orally three or even four times a day. This time, the research group also designed the sub-topic of key technology and industrialization platform of children’s sustained and controlled release preparations to explore and develop sustained and controlled release preparations suitable for children, and studied the oral absorption mechanism.

　　Children take drugs orally and through mucous membranes, such as nasal mucosa, rectal mucosa and lung mucosa, all of which are routes of administration. "The World Health Organization recommends that children use anal suppositories to reduce fever, but parents in China don’t accept it very well and children don’t like it." Wang Xiaoling said, this suggests that Chinese researchers can’t copy foreign experience. "We found that the gel dosage form is relatively easy to be accepted by parents, and the products developed now are highly accepted by parents. If you gently touch it, you can achieve good curative effect, and parents certainly welcome it. "

　　"Nothing reveals the soul of a society better than the way it treats its children." Wang Xiaoling always remembers such a famous saying, "All pharmaceutical workers do is to make children recover in sweetness."

　　Reporter Jia Xiaohong