Injection appeared relatively late, with a history of more than 100 years, while the injection developed with traditional Chinese medicine prescription was even later, with a history of only twenty or thirty years. However, the injection can be injected from intradermal, subcutaneous, muscle, acupoint, vein and spinal cavity, which opens up a new way for many drugs to exert their efficacy. Injection has developed into a large dosage form widely used all over the world, because this dosage form has its unique advantages and of course its disadvantages.
Advantages: ① rapid drug action and reliable effect. Injection is stored in liquid or powder form, but it is directly injected into human tissues, blood vessels or organs in liquid form in clinical use. So it absorbs quickly and acts quickly. Especially intravenous injection, liquid medicine can directly enter the blood circulation, which is more suitable for rescuing critical diseases. And because the injection does not pass through the gastrointestinal tract, it is not affected by the digestive system and food. Therefore, the dosage is accurate and the effect is reliable. ② Suitable for oral administration: Patients who often encounter coma, convulsion and spasm. Clinically, patients with digestive system diseases can't take medicine orally, but injection is an effective way of administration. ③ It is suitable for drugs that are not suitable for oral administration, and some drugs are not easily absorbed by gastrointestinal tract due to their own properties; Some are very irritating; Others are easily destroyed by digestive juice, which can be solved by making injection, in which the crystalline protein of Trichosanthes root is made into powder injection. ④ Other drugs can play a local role: for example, procaine hydrochloride injection can be used for local anesthesia; Xiaozhiling injection can be used for hemorrhoid injection, and ⑤ acupoint injection can play a unique role, such as angelica injection. ⑥ Injection is a liquid medicine or powder sealed in a special container and isolated from the outside air. It is sterilized or sterilized during the manufacturing process, so it is more storable than other liquid preparations.
Disadvantages: ① Pain during injection; ② It is inconvenient to administer drugs by injection; (3) Because the injection can't pass through the body's defense tissue (liver) like oral drugs, the quality requirements are stricter than other dosage forms, and improper use is more likely to lead to danger; ④ The manufacturing process is complicated. Therefore, drugs with good oral effect do not have to be made into injections.
As can be seen from the above characteristics, the advantages of injection are very prominent. As for the shortcomings of injections, due to the continuous development of modern medicine and the continuous innovation of production technology, the improvement of injection quality has been gradually overcome. Such as needleless injection, painless injection and automation and linkage in production, have created favorable conditions for overcoming its shortcomings and promoting its development.
(2) Development of traditional Chinese medicine injection.
There is no injection in the traditional dosage form of Chinese medicine. Because injections have many unique advantages, people began to develop traditional Chinese medicine injections decades ago. As early as 1930s, "Bupleurum Injection" was successfully developed to treat diseases such as cold and fever, and achieved good results. After the founding of the People's Republic of China, the development of traditional Chinese medicine injections was carried out in the mid-1950s. By the early 1960s, more than 20 varieties such as "*60 1 injection", "Yinzhihuang injection" and "20 1-2 (Radix Isatidis) injection" were developed for clinical use, and some of them were officially put into production and are still widely used today. Due to the continuous improvement of quality and stable curative effect, it has opened up a road for the development of traditional Chinese medicine injections.
Traditional Chinese medicine injection was a period of great development in the 1970s. Not only scientific research, teaching and production units have developed it, but also many urban and rural medical units have carried out trial production. According to statistics, traditional Chinese medicine injections have been clinically tried during this period. More than 700 species have been reported, and 23 species are recorded in People's Republic of China (PRC) Pharmacopoeia (1977 edition). Among them, there are dozens of good quality and reliable curative effects. For example, unilateral injections include Ding Gongteng, Aesculus schefflera, Ginseng, Radix et Rhizoma Rhei, Radix Sophorae Tonkinensis total alkaloids, Trichosanthis Radix, Radix Salviae Miltiorrhizae, Ilex pubescens, Radix Stephaniae Tetrandrae total alkaloids, Herba Euphorbiae Humifusae, Radix Angelicae Sinensis, Luying, Herba Houttuyniae, Herba Andrographis, Rhizoma Corydalis, Cornu Cervi Pantotrichum, etc. Compound injection contains Shengmai, Radix Angelicae Sinensis Carthami, Radix Bupleuri, Radix Isatidis, Xiaozhiling, Qingkailing, etc. Good clinical results have been achieved. Some of them have remarkable curative effects, have been mass-produced and have stable quality, which meet the clinical requirements of traditional Chinese medicine and are especially suitable for emergency treatment.
The quality control of traditional Chinese medicine injection is a key issue, because the injection is administered by injection and directly enters the body without being absorbed by the digestive tract, so the quality control must be strict. Traditional Chinese medicine injections are mostly extracted and refined from medicinal materials or decoction pieces. Objectively, there are many problems such as impurities, large differences in effective substances, and easy pyrogen. In recent years, a lot of in-depth research work has been done at home and abroad, and specific varieties have been tackled one by one. For example, the prescribed content determination standards of Trichosanthes root purified protein crystallization, Shengmai injection and Qingkailing injection are strictly pyrogen-tested; The stability experiments of rhubarb, Pulsatilla chinensis and baicalin injection were carried out. In addition, according to the characteristics of traditional Chinese medicine injections, a series of routine quality inspection items and standards have been stipulated, so that some traditional Chinese medicine injections can pass the quality test. It shows that traditional Chinese medicine injection, as a dosage form of traditional Chinese medicine, has been basically finalized and shows its unique advantages, which is a promising dosage form of traditional Chinese medicine. Especially in the development of Chinese medicine, it will be an indispensable main dosage form to solve the first aid of Chinese medicine. Not only will the variety of "small needles" be increased, but also the infusion will gradually pass the customs and then be put into production to meet the requirements of clinical medication of traditional Chinese medicine.
(3) Classification and application of injections.
1) is classified according to the physical state of dosage forms.
Liquid injection: also known as injection, commonly known as "water needle". It is a preparation made by preparing drugs into solutions (aqueous or non-aqueous), suspensions or emulsions and filling them into ampoules or multi-dose containers. Mainly according to the nature of drugs and medical requirements to determine. Generally, water-soluble drugs require quick response after injection, so they are often made into aqueous solution or hydrate solution (such as ethanol, propylene glycol, glycerol, etc. ). Some drugs should not be made into aqueous solution. If they are insoluble in water or the time after injection is prolonged, they can be made into oil solution, water or oil suspension or emulsion. But these injections are generally only for intramuscular injection.
Powder injection: commonly known as "powder injection". Some drugs have poor stability and are easy to decompose and deteriorate after being made into solutions. Generally, these drugs can be sterilized by aseptic operation, and sterile powder drugs for injection can be packed in ampoules or other suitable containers, and dissolved or suspended with appropriate solvents when used. Such as penicillin, streptomycin, phenobarbital sodium, etc., can be made into "powder injection". In recent years, a number of traditional Chinese medicine injections have been successfully developed at home and abroad, such as refined crystalline toxic protein extracted from Trichosanthes root, ginseng extract, refined pueraria decoction and so on. There are also some drugs, such as enzyme preparations (trypsin, α chymotrypsin, boron protease, coenzyme A, etc. ), often freeze-dried under aseptic operation to make powder injection. Some biological products are also made into powder for injection by freeze-drying, such as placenta albumin powder for injection.
Tablets for injection: refers to the molded tablets or mechanical tablets made of drugs after aseptic operation, which are dissolved in water for injection and used for subcutaneous or intramuscular injection, such as morphine hydrochloride tablets for injection. But at present, this kind of preparation is rarely used.
2) Classification by management site
Intradermal injection: Injection between epidermis and dermis, usually in forearm. The dose of a needle is below 0.2m 1, which is often used for allergy test or disease diagnosis, such as toxin skin test solution and diphtheria diagnostic toxin.
Subcutaneous injection: it is injected into the soft tissue between dermis and muscle, and the injection site is mostly outside the upper arm. The general dosage is 1 ~ 2m 1. Subcutaneous injection is mainly aqueous solution, but the drug absorption rate is a little slow. Because people's subcutaneous sensation is more sensitive than muscle, the suspension of irritating drugs and oil or water is generally not suitable for subcutaneous injection. Sometimes the patient's blood vessels are difficult to find or for other reasons, large-dose infusion can also be dripped subcutaneously.
Intramuscular injection: it is injected into muscle tissue, and the injection site is mostly in arm muscle or upper arm deltoid muscle. The stimulation of intramuscular injection is less than subcutaneous injection, and the injection dose is generally 1 ~ 5m 1. Besides aqueous solution, intramuscular injection can also inject oil solution, suspension and emulsion. Oil injection can be absorbed slowly and evenly in muscles, which can play a delaying role.
Intravenous injection: intravenous injection enables drugs to enter the blood directly, so it has the fastest effect and is often used for first aid, supplementing body fluids and nutrition. Due to the large amount of blood vessels, high-dose intravenous injection is also called "infusion". A dose varies from a few milliliters to several thousand milliliters, and most of them are aqueous solutions. Oil solution and general suspension or emulsion can cause capillary embolism, so intravenous injection is not allowed. However, in recent years, studies have shown that some emulsions made of nutritional drugs and medicinal oils can accelerate the absorption of drugs through intravenous injection. The oil droplets of these emulsions should be smaller than red blood cells, with an average diameter below 65438±0 μm m. Due to the buffering effect of blood, a small amount of slow injection has little effect on the PH value and osmotic pressure of blood. If the injection volume is large, the PH value and osmotic pressure should be considered. Intravenous injection is more effective than subcutaneous or intramuscular injection, and any liquid medicine that can dissolve red blood cells or precipitate protein should not be given intravenously. Therefore, antibiotics should not be added to intravenous injection in general.
Spinal cavity injection: injected into the subarachnoid space around the spine. Because nervous tissue is sensitive, spinal fluid circulation is slow. Therefore, the injection dose should not exceed 10ml at a time, and the purest aqueous solution should be used, with the PH value between 5.0 and 8.0 and the osmotic pressure the same as that of spinal fluid. Otherwise, due to osmotic pressure disorder or other effects, it will soon cause adverse reactions such as headache and vomiting. In a word, the preparation and application of intraspinal injection should be strictly required.
Powder injection and other injections:
Powder injection:
Sterile powder for injection prepared by aseptic operation is called powder injection. All drugs that are sensitive to heat or unstable in aqueous solution, such as some antibiotics (penicillin G potassium, streptomycin, polymyxin) and pharmaceutical enzyme preparations (trypsin, coenzyme A, etc. ), which can neither be made into general water-soluble injection nor sterilized by heating in aqueous solution, can only be made into powder injection through aseptic operation and dissolved in appropriate injection solvents before clinical use.
The preparation methods of powder injection can be divided into two types according to the properties of drugs:
① Refine the raw materials into sterile powder, and carry out aseptic packaging under aseptic conditions.
(2) making the medicine into sterile aqueous solution, filling it aseptically according to the conventional method, freeze-drying, and sealing it under aseptic conditions.
Suspension injection:
A drug for intramuscular or intravenous injection made by dispersing insoluble solid drugs in a liquid dispersion medium is called suspension injection. In recent years, according to the needs of clinical medication, such drugs can be administered by intravenous route, which can better play the role of drugs. The reticuloendothelial system in human body has the function of swallowing foreign bodies. If water-insoluble solid drugs are made into intravenous granules, they are sent into the body through veins and stored as foreign bodies in areas rich in reticuloendothelial cells, so as to increase the drug concentration there, thus achieving the purposes of improving the curative effect, reducing the dose, prolonging the drug effect (the drug is gradually absorbed) and reducing the side effects. Therefore, for the lesions of reticuloendothelial system (such as liver and lymph), intravenous suspension can obtain better curative effect than general injection. For example, in China, camptothecin with anticancer effect is made into suspension for intravenous injection, which makes the drug highly concentrated in the liver and has achieved satisfactory results in the treatment of liver cancer.
Under the following circumstances, drugs can be made into suspension injections, that is, insoluble solid drugs that can be dissolved without appropriate solvents; Drugs that need to be made into long-acting preparations; This drug needs to be made into high-content injections. However, it must be pointed out that the above situation must be based on the premise that solid drugs can be absorbed by the human body.
Suspension injection has the following special requirements in dosage form:
Strictly control the size of drug particles. For general injections, the particle size should be less than 15μm, and 1520μ m should not exceed10%; For intravenous injection, the particle size is less than 2μm, accounting for 99%. Otherwise, it will cause venous embolism. It has good dispersibility and will not settle too fast. Once it sinks during storage, it can be redispersed by shaking without caking. It has good needle penetration. It can be easily taken out of the bottle by subcutaneous injection of the needle and will not stick to the bottle wall. Should be sterile and pyrogen-free.
Ophthalmic solution:
Any liquid preparation used for eye washing or eye drops to treat or diagnose eye diseases is called eye drops. Most of them are true solutions or colloidal solutions, and a few are suspensions. According to its usage, it can be divided into eye drops and eye drops.
Eye-washing agent: the drug is prepared into a sterile aqueous solution with a certain concentration, which is used for eye washing and cleaning. Such as physiological saline, 2% boric acid solution, etc.
Eye drops: refers to the clear solution or suspension of eye drops. It is often used for sterilization, anti-inflammation, convergence, pupil contraction, anesthesia or diagnosis. Some can also be used to smooth or replace tears.
The eye is the most delicate organ of human body, and the quality of eye drops is directly related to the health of patients. Its quality requirements are similar to those of injections, and there are corresponding requirements for pH value, osmotic pressure, sterility and clarity, but the strictness is different. The specific requirements are as follows:
(1)PH value has an important influence on eye drops. Stimulation caused by improper PH value can increase the secretion of tears and lead to the rapid loss of drugs. Even the solution that damages the cornea has the least irritation to the eyes, and there is no uncomfortable feeling at pH 6 ~ 8. However, many drugs are unstable under neutral or alkaline conditions, so it is necessary to give consideration to curative effect, minimum stimulation and drug stability.
On the other hand, controlling proper PH value can increase the therapeutic effect of drugs. Many drugs, especially the salts of alkaloids, are inseparable from free alkali in a suitable pH range (pH7 or above). Free alkali is fat-soluble and can penetrate into the cornea, thus improving the curative effect.
(2) The osmotic pressure of osmotic pressure eye drops should be similar to that of tears to reduce irritation. The range of osmotic pressure that eyeball can adapt to is equivalent to 0.6 ~ 1.5% sodium chloride solution, and there is obvious discomfort when it exceeds 2%. Appropriate drugs, such as sodium chloride and boric acid, should be used to make the hypotonic solution isotonic.
(3) Whether there is trauma in sterile eyes is the limit of the strictness of aseptic requirements for eye drops. Ophthalmic preparations used after corneal injury or intraocular surgery must be sterile and packaged in a single dose. Normal people's tears contain lysozyme, which has bactericidal effect. At the same time, tears constantly wash away the eyes to keep them clean and sterile. Cornea, sclera, etc. It can also prevent thinning.
Bacteria invade the eyeball, but these protective measures disappear after eye damage or surgery. Therefore, for patients with ocular trauma, the ophthalmic preparations used should be absolutely sterile and the finished products should be strictly sterilized. Antibacterial agents are not allowed to be added to this ophthalmic preparation, and once it is opened, it cannot be placed for reuse. For patients without eye trauma, the eye drops used should be free of pathogenic bacteria, Pseudomonas aeruginosa and Staphylococcus aureus. In order to prevent patients from being infected with bacteria after repeated use, bacteriostatic agents should be added to the finished product.
(4) The clarity should be clear and free of foreign objects, especially broken glass, because it will cause eye injury and infection. The particle size of suspension eye drops should be less than 50 μ m.
(5) Increasing the viscosity of eye drops with proper viscosity can keep moisture, prolong the contact time between liquid medicine and eye tissues, and enhance the curative effect of drugs. A suitable viscosity is between 4 and 5 cpa.s ..