Capsules usually refer to solid preparations made by filling drugs into hard hollow capsules or elastic sealed soft capsules. Empty capsules are usually made of gelatin. Capsule has a long history. As early as BC 1500, the first capsule was born in Egypt. 1730, pharmacists in Vienna began to make capsules with starch; 1834, the capsule manufacturing technology was patented in Paris; 1846, two-stage hard capsule manufacturing technology was patented in France; 1872, the first capsule filling machine was born in France. 1874, Detroit, USA started the industrial manufacture of hard capsules, and introduced various models at the same time. Taking medicine with capsules can avoid discomfort and make the medicine easy to swallow. Its outer coating can also ensure the stability of the drug, avoid moisture absorption and photolysis, and prolong the shelf life. More importantly, the outer coating can also play a great role in controlling the release rate of drugs or locating organs in vivo and improving the bioavailability of drugs. At the same time, it can also reduce the stimulation of drugs to esophagus and gastric mucosa, as well as the reduction of drug efficacy and the loss and waste of drugs. Because capsules will enter the human digestive system and be absorbed together with drugs, medicinal hollow capsules are usually managed according to pharmaceutical excipients. In this regard, some relevant laws and regulations promulgated in China have made clear requirements, and European and American countries also have legal standards for capsules. According to the European Union's legal provisions on pharmaceutical products, the ingredients of all excipients, including capsules, must be clearly stated in the marketing authorization before listing. According to American law, drugs include not only finished drugs, but also active ingredients, excipients and other ingredients. Therefore, capsules should also be regulated like medicines. The bad thing about this "problem capsule" incident is that some capsule manufacturers who were investigated evaded inspection by various means, and used industrial gelatin processed from tanned leather scraps instead of edible gelatin as raw materials to make medicinal capsules. This kind of capsule with seriously excessive chromium content will do harm to human body. How to identify "problem capsules"? Mainly grasp the following two points: look at the color. Edible gelatin is usually transparent, colorless and relatively pure, while industrial gelatin will be covered with more flavors and dyes because of its many impurities, and its color will be darker. Look at the texture. The quality of capsules made of general industrial gelatin is poor, the shell is fragile and easy to break, and many capsules are loose or have thin seams, which are easy to unscrew. Most hollow capsules of medicines and health products are made of gelatin. Gelatin is a water-soluble protein mixture, which is produced by partial hydrolysis or boiling of collagen in animal skin, ligaments and tendons with acid or alkali. After bone soup is concentrated at home, the surface of the soup will appear clear and transparent, almost pale yellow frozen, which is gelatin. Nowadays, gelatin exists in many common and favorite foods, such as frozen skin, canned meat, cotton candy and so on. It can be gelled, thickened, stable and breathable. Gelatin has many characteristics, such as gelation, water retention, cohesiveness and solubility, which also make it widely used in pharmaceutical industry, the most important of which is to make capsules, replace plasma and coat. China Pharmacopoeia stipulates that the raw material gelatin used in the production of medicinal capsules should at least meet the standard of edible gelatin. According to the industry standard of edible gelatin in China, edible gelatin should be made from animal skins and bones, and it is forbidden to use any industrial waste after tanning in tanneries. However, according to CCTV's Weekly Quality Report, some gelatin producers in Hebei, Jiangxi and other places bought scraps from leather cutting at low prices. These leather scraps are first treated with quicklime, then neutralized and decolored with industrial strong acid and alkali, cleaned and boiled into glue solution in a glue boiling pot. The boiled transparent glue, after being concentrated, gelled, dried and crushed, becomes a light yellow so-called "blue leather glue". In fact, this kind of gelatin is industrial gelatin which is prohibited by the state as a raw material for food and medicine. Gelatin can be divided into food, medicine and industry according to its use. In these three categories, the raw materials of food and medicine are very strict, all have national standards, and they are mandatory national standards. However, the detection technology of industrial gelatin in China is still blank. In the List of Non-edible Substances and Food Additives Easily Abused in Foods issued by the Ministry of Health, industrial gelatin is listed impressively, pointing out that it may be added to foods such as ice cream and jelly, but it is indicated that there is no detection method, and sometimes it is difficult to distinguish medicinal gelatin, edible gelatin and industrial gelatin in appearance (especially when mixed). Undoubtedly, the lack of detection methods and the huge profits have led to the possibility of illegal use of industrial gelatin. Because tanning agents containing chromium are used in industrial tanning, chromium slag often appears. When this kind of industrial leather waste is used to make industrial gelatin, the chromium content will generally exceed the standard. Chromium exists widely in nature, with trace amounts in animals and plants, and 6 ~ 7 mg in normal people. From the point of view of nutrition, chromium is an essential trace element for human body. It is an important part of glucose tolerance factor in the body and also participates in regulating lipid metabolism. Chromium deficiency may cause problems in blood sugar control. Once absorbed by the human body, chromium quickly leaves the blood, and most of it is distributed in various organs. It is excreted mainly through the kidneys. Generally speaking, a healthy adult's ability to excrete chromium through the kidney can reach about 0.2 mg per day. Excessive storage of chromium in the body may produce toxic effects, irritate and corrode the skin and mucosa, and lead to dermatitis, ulcer and pharyngitis. In severe cases, protein may precipitate in human blood, causing anemia, nephritis, neuritis and other diseases. If ingested in large doses for a long time, it may cause kidney damage, and may also have mutagenic and carcinogenic effects. So, how much chromium is safe for human body to consume every day? According to the reference intake of dietary nutrients for China residents formulated by China Nutrition Society, the recommended daily intake of chromium is 0.0 1 mg for children and 0.05 mg for adults, and the safe maximum tolerated dose is 0.2 mg for children and 0.5 mg for adults. China Pharmacopoeia (version 20 10) clearly stipulates that the content of heavy metal chromium in medicinal capsules and gelatin raw materials used shall not exceed 2 mg/kg (that is, 2 parts per million). This limit is actually to use chromium as a marker to prevent industrial leather scraps from mixing with the raw materials for making capsules. At present, China Pharmacopoeia has the strictest standard for hollow capsules. Some medical experts pointed out that from the existing information about the safety of chromium, the maximum content of chromium in capsules reported recently and the number of capsules taken by patients every day, it is generally believed that it will not cause acute chromium poisoning and chronic chromium accumulation in human body. However, some medical experts have warned that the chromium in capsules exceeds the standard, which is more like a weather vane. Because in the process of leather tanning, leather may go through depilation, anti-corrosion, polishing, dyeing and other links, and the hazards of various chemicals used are difficult to assess, which can not be covered by one chromium poisoning. After the exposure of the "problem capsule", the public was worried, and "new" ways of taking various capsule medicines were also "invented": steamed bread, glutinous rice balls, bananas, cucumbers ... and even taking them without taking capsules. However, these "new" ways of eating met with strong opposition from pharmaceutical experts. Because capsule and powder are not the relationship between dumpling skin and stuffing. Capsule is not a device for simply filling powder, and its role in exerting drug effect is irreplaceable. If the capsule medicine is peeled off and eaten casually, it may not only stimulate the human mouth, esophagus and stomach, but also affect the efficacy. Drugs are essentially chemical molecules that affect the body, which is also the original purpose of applying drugs. According to the physical and chemical properties, pharmacological effects, routes of administration and the need to adjust the absorption rate of drugs, the drugs are made into different dosage forms. The same drug can also have different dosage forms, which are suitable for different routes of administration and have different curative effects. In other words, in order to realize the safety and effectiveness of drugs in human body, and then achieve the timely, quantitative and local control of drugs, it is necessary to make drugs into a specific dispersion system. In fact, according to different clinical uses and functions, various special types of capsules have appeared, such as enteric-coated capsules, sustained-release capsules, effervescent capsules, inhalation capsules and capsules for intraluminal administration. Enteric-coated capsules are hollow capsules filled with drugs or contents (granules, pellets, etc.). ) coated with enteric coating, and then filled into hollow capsules to release drugs in intestinal juice. For example, azithromycin enteric-coated capsules are suitable for intestinal release. In addition, some drugs contact with gastric juice will greatly affect the efficacy, which needs to be disintegrated in the intestine, which also needs to be wrapped in specially designed capsules to resist the dissolution of gastric acid. Sustained-release capsule refers to the preparation that drugs are made into contents with sustained-release effect through a certain process and then filled into hollow capsules. Take Fenbid as an example, its drug packaging box is marked with "slow-release capsules", which means that the slow release of drugs can be controlled according to the design requirements.