Knowledge Manual Herbal Formula Granule

Chinese Medicine Formula granules are single-flavor granules made of high-quality Chinese medicine tablets that meet the preparation specifications as raw materials, and are extracted and concentrated by modern high-tech. 

Its sexual taste and efficacy are consistent with the original drugs, which are used for the clinical formula of traditional Chinese medicine, and have the advantages of no need to decoct, directly brew, small dosage, accurate efficacy, health and safety. 

Such as licorice formula granules, yellow lotus formula granules, angelica formula granules, banlan root formula granules and other more than 500 kinds of commonly used Chinese Medicine formula granules. 

Decoction is the earliest and most widely used dosage form in traditional Chinese Medicine. it can adapt to the principle of Chinese medicine to distinguish and treat, with the principle of adding and subtracting with the interpretation, with the characteristics of rapid absorption and rapid exertion of medicinal effects, and is still the main way of medication in Chinese medicine. 

With the progress of the times and the acceleration of the pace of life, people have put forward new requirements for Chinese medicine. Many patients have given up Chinese medicine treatment because they are unwilling to decoct Chinese Medicine.

Solving the problems of quality stability, convenience, and safety of traditional Chinese Medicine decoctions is extremely urgent.   

(1) The quality of the decoction is affected by the quality of Chinese herbal medicines and the method of decoction of the patient, and the quality is not well controlled.  

The quality of decoction pieces of traditional Chinese Medicine is affected by many factors such as the variety of medicinal materials, place of origin, harvesting season, processing and storage, and the quality varies greatly. Improper storage often causes moth-eaten, mildew, and oil loss; irregular processing and loss of active ingredients; impurities mixed in during transportation and drying; even selling counterfeit or non-genuine or substitutes, while medicinal materials are in circulation.

The link lacks advanced inspection equipment, and it is difficult to distinguish the quality of the authenticity. The patient's own decoction is not standardized, and it is difficult to grasp the requirements for decoctions such as decoction utensils, decoction water, decoction times, water addition, decoction time, fire time, decoction first, decoction after decoction, and candle preparation . 

A large number of experimental reports have proved that home-style decoction can only decoct 50% to 70% of the effective ingredients in the medicinal materials, which is a serious waste of medicinal materials.  

Traditional Chinese medicine decoction is time-consuming to decoct and consume a large amount. It is also inconvenient to carry and store. It is difficult for people who go to work, school, travel, or travel to take the decoction. 

Traditional Chinese medicine doctors often encounter that after the prescription is completed, the patient goes back and says that there is no time to decoct the medicine, no conditions to decoct the medicine, and request to switch to Chinese patent medicine or western medicine. As a result, the use rate of decoction is declining year by year. 

According to a survey conducted by the Chinese Traditional Chinese Medicine Research Institute, 70% of the annual consumption of medicinal materials in the early days of liberation was used for the preparation of decoctions and 30% for the production of finished medicines. In 1993, the proportion of species was completely reversed, and the gap is still widening. 

In foreign countries, especially in western developed countries, traditional Chinese medicine has received more and more attention and has gradually gained recognition in many countries. Medical practices in foreign countries have also shown that traditional Chinese medicine decoctions are effective. 

However, Westerners are unacceptable to the way patients use traditional Chinese medicine to decoct themselves. One is that they are unacceptable conceptually, and the other is that the forms of medication do not fit their lifestyles. 

Japan produced more than 200 kinds of "Kanfang granules" for graduate students in the 1970s. In the 1980s, Taiwan also produced more than 400 kinds of "scientific Chinese medicine" and more than 300 classic prescription granules. 

"Hanfang Granules" and "Scientific Chinese Medicine" are widely used in Europe, America, Southeast Asia and other places and are very popular. South Korea began to study single-flavored Chinese medicine concentrate granules in the early 1990s and produced more than 300 varieties. 

Although China's export volume of Chinese medicinal materials ranks first in the world, it rarely undergoes deep processing and has extremely low added value, accounting for only about 4% of the world's total natural medicine trade. It is not as good as Japan's "Heart Relief Pill" and South Korea's "Ginseng Ginseng". 

"Scientific Chinese medicine" produced in Taiwan is sold in the United States many times higher than that of decoction pieces, and has achieved great economic benefits. This situation not only provides us with a good opportunity for Chinese medicine to go global and participate in international competition, but also makes us face an arduous challenge on how to seek our own development and adapt to the needs of the international market. 

The former Minister of Health of China Chen Minzhang gave instructions to the project: "Accelerate and strengthen the progress of scientific research in this field in order to serve clinical and production services as soon as possible. The rapid development of foreign countries in this area deserves our high attention! This should be Our advantage". 

In May 1993, the State Administration of Traditional Chinese Medicine organized the investigation, research and demonstration of the scientific research project of traditional Chinese medicine formula granules. In December 1993, the scientific research project of traditional Chinese medicine formula granules was established as a major scientific research project of the State Administration of Traditional Chinese Medicine.  

(1) Yifang Pharmaceutical is the earliest unit in China to carry out research on traditional Chinese medicine formula granules. After more than ten years, it has conducted a large number of basic research and clinical research and has achieved fruitful scientific research results.  

(2) Yifang Pharmaceutical has the Guangdong Institute of Traditional Chinese Medicine as a strong technical support. For more than ten years, Chinese medicine formula granules have been the core research project of the institute. With the support of the national, provincial and municipal governments at all levels, Yifang Pharmaceutical has been in a leading position in the technology and product promotion of the project.  

(3) As a key scientific and technological project of Guangdong Province, the Chinese Medicine Formula Granules project has attracted the attention of the Guangdong Provincial Government, especially the Provincial Administration of Traditional Chinese Medicine. In order to coordinate the development of the project, a project coordination leading group and an expert group headed by the deputy director of the Provincial Department of Health have been established to provide technical and policy guarantees for the technical public relations and promotion of the project.  

(4) In the project expert appraisal meeting organized by China Food and Drug Administration in 2001, Yifang Pharmaceutical's technical achievements were widely praised by experts, and the total assessment score ranked first.  

(5) The product quality, clinical efficacy and market service of Yifang Traditional Chinese Medicine Formula Granules have been recognized in the Chinese and international markets, and the brand of Yifang Formula Medicine has been established.  

The production of Chinese medicine formula granules is based on the decoction requirements of Chinese medicine decoctions, and the production process specifications are formulated according to different varieties. 

The basic process route is: optimization of Chinese medicinal materials, processing, extraction, concentration, drying, granulation, packaging, and inspection.  

The traditional Chinese medicine formula granules are similar to the traditional decoction decoction method. It is based on inheriting the traditional decoction method, combined with modern science and technology research and production. 

Mainly manifested as: 

(1) The extraction process of traditional Chinese medicine formula granules is in accordance with the requirements of traditional decoctions. Such as the amount of water added, soaking time, the number of times of decoction, first decoction, second decoction, package decoction, decoction, melting, another decoction, brewing and so on. Combined with the use of modern scientific and technological means, research and optimization of the extraction technical parameters of different Chinese medicine varieties.  

​(2) Combine the latest research results of modern Chinese medicine chemistry, Chinese medicine pharmacology, and Chinese medicine pharmacy. For the fat-soluble active ingredients that have been clearly studied, water extraction combined with ethanol extraction, supercritical carbon dioxide extraction and other technologies are used to fully extract the active ingredients.  

(3) For the varieties traditionally used as medicines in powder. Using ultra-fine crushing technology, the plant cell wall is broken and the drug effect can be quickly exerted.  

(4) In the granule manufacturing process, the extract powder is directly compressed into granules without adding excipients. Some varieties do need to add excipients, and they should be added as little as possible. Therefore, Chinese medicine formula granules are different from other granules. 

At present, the clinically commonly used granules and granules contain excipients and a small amount.  

The first decoction is to increase the decocting time of the medicine, the purpose is to increase the dissolution of the effective ingredients in the water, reduce the toxicity of the medicine, and give full play to the efficacy of the medicine. 

Such as gypsum, calcined natural copper and other minerals: stone cassia, oysters and other shellfish: tortoise shell, turtle shell and other class A drugs: aconite, aconite and other toxic drugs: dendrobium, Tianzhuhuang, etc. 

The research on the production process of this kind of formula granules is to optimize the process parameters through the method of orthogonal experiment. 

For example, dendrobium needs to be decocted twice for a total of 4 hours; tortoise shell sand is fried and broken, and then decocted twice with water for a total of 10 hours. This is something that cannot be done by family decoction.  

The main varieties to be fried are: tortoise shell, turtle shell, gypsum, natural calcined copper, ochre, cold water stone, keel, amethyst, oyster, cassia cassia, Chuanwu, Caowang, aconite, dendrobium, Tianzhu yellow, talc, Magnet, mother-of-pearl, actinolite, red stone fat, etc. 

The next step is to reduce the decocting time of the medicine. The purpose is to reduce the loss of volatile oil and avoid the decomposition and destruction of effective ingredients. 

 It has a fragrant smell and contains drugs with a lot of volatile oils, such as peppermint, nepeta, Amomum villosum, patchouli, cardamom, artemisia annua, etc. 

First collect the volatile oil by distillation or use supercritical CO2 to extract the volatile oil, and then add water for extraction. After the volatile oil is dehydrated, it is wrapped and added to the granules. 

Drugs that are not easy to decoct for a long time, such as Uncaria, Rhubarb, etc., are extracted by cold extraction. 

The following varieties are mainly: mint, nepeta, amomum, patchouli, cardamom, artemisia annua, cassia twig, perilla, elm, parsnip, angelica, scallion, chrysanthemum, peony bark, forsythia, houttuynia, Xu Changqing, rose Flowers, Uncaria, Senna, Rhubarb, etc.  

Traditional Chinese medicine decoction has always emphasized proper heat. Just as Li Shizhen said, "If the fire is inappropriate, the medicine will have no effect", and emphasized: "First martial arts and then literary, if the law takes it, there is no ineffectiveness" Wu Huo means emergency fire. 

The actual firepower is inseparable from the amount of water and time. For example, the wind-relieving medicine is generally fragrant and highly volatile. At this time, it is required not to add too much water, the firepower should be large, and the decoction time is short, so that the decoction will smell fragrant. Perspiration has a strong effect on relieving the surface, and it can take effect quickly after taking it.  

The production of traditional Chinese medicine formula granules is to realize the fire control of traditional decoction by controlling the steam pressure and temperature during extraction. 

Nourishing and conditioning medicine. Generally, the texture is tough and viscous (mostly roots and stems), and it is not easy to fry the effective ingredients for a while. At this time, you need to add more water. 

At the beginning, use high fire to boil, then switch to low fire for slow frying , The time should be long, so that the decoction of the concoction will have a thick and thick flavor, obvious nourishing effect, and lasting power after taking it. 

The production of traditional Chinese medicine formula granules is to realize the fire control of traditional decoction by controlling the steam pressure and temperature during extraction. 

The production of animal medicines is based on different varieties, using processes such as crushing, decoction, and enzymatic hydrolysis. 

Mineral medicines adopt different processing techniques according to the classification of raw and calcined use. The extraction method still follows the requirement of traditional decoction for a long time. Such as plaster, natural copper, magnet, keel. 

Donkey-hide gelatin should be treated separately in the decoction. Generally, it should be stewed with yellow wine or steamed with water. After the other medicines are decocted and the dregs of the medicine are removed, add the decoction and take it together. 

Ejiao should not be decocted with other medicines, otherwise it will easily adhere to the bottom of the medicine tank, and it will be scorched easily, which makes it difficult to exert its effect. Ejiao is steamed separately in water, which takes a long time and brings inconvenience to the patient's decoction. 

Ejiao formula granules are first stewed in water, centrifuged at high speed, atomized and dried into powder, and can be taken with boiling water. It is effective and convenient to take it separately or add it to the decoction. 

"Materia Medica" contains: 

"Rhubarb is used raw for those who desire fast, swallowed in the soup; for those who desire slow down, use it with medicine and decoction." The purgative component of raw rhubarb combined with onion wake is destroyed by thermal decomposition, and it is taken after clinical use or soaked in boiled water. 

The production process of rhubarb formula granules adopts cold extraction method to ensure that the heat-sensitive active ingredients are not damaged. 

The research on the production technology of Chinese medicine formula granules is based on inheriting the traditional decoction method, combined with the research results of modern Chinese medicine chemistry, Chinese medicine pharmacology, and Chinese medicine pharmaceuticals, using water extraction. 

Water extraction combined with ethanol extraction, supercritical carbon dioxide extraction, and enzymatic hydrolysis Advanced Chinese medicine pharmaceutical technology such as technology, ultra-fine pulverization, low-temperature concentration, spray drying, and dry granulation. 

Ultrafine pulverization of Chinese medicine mainly refers to cell-level pulverization, so that Chinese medicine is pulverized to a few microns or even smaller. Some precious medicinal materials and Chinese medicines that are used clinically as powders, such as antelope horn, panax notoginseng, fritillaria, agarwood, centipede, scorpion, etc., are made into a new generation of micron Chinese medicines using modern Chinese medicine cell ultra-fine pulverization technology. 

The particle size of the powder of micron Chinese medicine is about 5-15 um. Under this fineness, the cell wall ratio of the medicinal material is ≥95%, and the powder diameter is small, the distribution is uniform, the sphericity and homogeneity are obviously improved, and the honeycomb degree and ratio The surface area is significantly increased. As a result, the change in the physical state obviously makes the human body absorb the components more comprehensively, the absorption strength is improved, and the absorption volume is increased. 

Mainly manifested as:  

(1) The dissolution and release of the effective ingredients of the drug are accelerated. Because the ultrafine powder has a small diameter, high wall-breaking rate and exposed active ingredients, after entering the body, the soluble components can be quickly dissolved and released. Even the low-solubility components have a larger size due to the ultrafine powder. Adhesive force and tightly adhere to the intestinal wall, and its effective ingredients will be quickly absorbed through the intestinal wall and enter the blood. Moreover, due to the influence of adhesion, it takes longer to expel the body, thereby increasing the absorption rate of the drug. In this way, the dissolution rate and release rate of the effective ingredients of the ultra-finely pulverized drug are faster than those of ordinary pulverized powder.  

(2) The dissolution rate of the active ingredient of the drug is accelerated. The dissolution rate of the active ingredient of the drug is proportional to the specific surface area of ​​the crushed drug. The smaller the particle size, the larger the surface area and the larger the effective contact area with gastrointestinal body fluids, which is more conducive to the dissolution and absorption of the drug. That is, the dissolution rate and absorption rate of the active ingredients of the drug increase with the decrease of the particle size of the drug particles. After the Chinese medicinal materials are ultra-finely pulverized, due to their fine and uniform particle size, increased specific surface area, increased porosity, enhanced adsorption and solubility, and increased dissolution rate and chemical reaction rate, the drug can be better dispersed and dissolved in the gastric juice , Is conducive to the absorption of drugs, thereby improving the therapeutic effect.  

(3) The pharmacodynamic activity of the drug is improved. The solubility of the drug powder after ultrafine pulverization and the types of active ingredients released increase, the biological body’s absorption efficiency of the active ingredients per unit time is improved, the drug onset time is shortened, and the action time is prolonged, so the effect on the body is more effective. Full and stronger. There are no intact tissue cells in the observation of the superfine Notoginseng powder with electron microscope, light yellow, brown, and brown irregular small particles are full of the field of view, the diameter is 7-14 um, calcium oxalate cluster crystals are not easy to distinguish, and there are no large particles and clumps. Cell morphology exists. 

It shows that all kinds of cells in the panax Notoginseng tissue have been destroyed, and various components in the cells have been released. 

The varieties of traditional Chinese medicine formula granules that use ultra-fine grinding technology are: Jinsha Niu, Antelope Horn, Ganoderma lucidum, Whole Scorpion, Panax Notoginseng, Buffalo Horn, Gastrodia, Centipede, American Ginseng, Blood Scorpion, Fritillaria, Purple River Car, Chuan Fritillaria , Paoshanjia, Amber, etc. 

Supercritical carbon dioxide extraction is a new type of technology for supercritical carbon dioxide fluid extraction and separation of the effective components of traditional Chinese medicine.  Supercritical carbon dioxide extraction (SFE-CO2) has the advantages of good selectivity, low operating temperature, effective components not being destroyed during the extraction process, no secondary biochemistry, strong extraction capacity, anti-oxidation, and sterilization. 

We compared more than 30 kinds of traditional Chinese medicines containing volatile oil with SFE-CO2 extraction and steam distillation. The oil yield of SFE-CO2 method is 3.8-11.4 times higher than that of steam distillation, and the oil quality is improved. For example, the odorifer oil collected by steam distillation is a light yellow oily liquid and lacks the characteristic aroma of odoriferous odorifera. The odoriferous oil extracted by SFE-CO2 is orange-yellow at room temperature, with obvious aroma of odorifera, and the effective ingredients are fragrant. 

The absolute amount of Cyperene is greater than that of steam distillation. The medicinal materials such as Angelica dahurica, Angelica, Ligusticum chinensis, Bupleurum in Umbelliferae family all contain volatile oil, and the yield of volatile oil extracted by steam distillation is very low. The yield of SFE-CO2 extraction of the volatile oil of Angelica sinensis was 1.5%, and the yield of the volatile oil of steam distillation was 0.01%. SFE-CO2 extraction of Ligusticum chuanxiong, the yield of volatile oil was 3.75%, while the yield of steam distillation was only 0.015%. 

The GC-MS analysis showed that the volatile components of the traditional Chinese medicine formula granules prepared by the two methods were also different. The absolute amount of ligustilide (Ligustilide) in the granules prepared by the SFE-CO2 method was greater than that of the steam distillation method.  Dan Ginseng IIA is one of the effective and soluble ingredients of Dan Ginseng ester. 

The Pharmacopoeia stipulates that its medicinal materials contain dansine IIA (C19H18O3) not less than 0.2%. Using ethanol extraction, the negative rate of tanginone IIA detection is higher. This is mainly because the tanginone alcohol extract is processed into a dry paste powder through various processes. The tanginone IIA has been chemically degraded, and the degradation rate is less than that of water and heat. closely related. SFE-CO2 extraction is adopted, which has high effective ingredient content and low impurity content. The content of tannin IIA in the extract is more than 20%. 

The total pigment of hydroxynaphthoquinone is one of the fat-soluble components in Xinqiang Lithospermum. The pharmacopoeia stipulates that the total pigment of hydroxynaphthoquinone in its medicinal materials shall be calculated as levorpin (C16H16O5), not less than 0.8%, SFE-CO2 extraction efficiency is high , The extract is purple in color. Dehydroandrographolide (C20H26O4) and Andrographolide (C20H30O5) are the effective ingredients in Andrographis paniculata, and the pharmacopoeia stipulates that the total amount of the two in their medicinal materials shall not be less than 0.8%. Andrographolide and dehydroandrographolide are unstable when exposed to heat and are easily destroyed by water and alcohol extraction. SFE-CO2 extract contains 19% lactone and 12% dehydroandrographolide.  Supercritical carbon dioxide extraction of volatile, fat-soluble, and heat-sensitive active ingredients in medicines has great advantages. 

We use SFE-CO2 extraction for 38 varieties containing lipophilic and heat-sensitive ingredients to improve the quality, clinical efficacy and stable quality of the formulated granules.  For medicinal materials containing water-soluble ingredients and fat-soluble active ingredients such as angelica, we select medicinal materials from different origins and different batches, and use a combination of water extraction and supercritical carbon dioxide extraction. 

The particles are subjected to gas chromatography (GC). Obtain the fingerprint of volatile oil, use high performance liquid chromatography (HPLC) for the water-soluble components, obtain the fingerprint of the water-soluble components, count the chromatographic peaks, and use them as chemical characteristic variables, respectively, with burburnum lactone and ferulic acid as reference materials Analyze the obtained data systematically and formulate the standard fingerprint of Angelica formula granules, which can identify and evaluate the authenticity of Angelica formula granules without the shape of decoction pieces, which is comprehensive and advanced. 

The production of Chinese medicine formula granules adopts supercritical extraction combined with water extraction technology. 

The varieties are: 

Angelica dahurica, Atractylodes macrocephala, Piper longum, Atractylodes, Cao Guo, Bupleurum, Ligusticum chuanxiong, Angelica, Angelica guinea, Radix edulis, Zedoary turmeric, Fangfeng, Bergamot, dried ginger, Huben, Magnolia officinalis, Zanthoxylum bungeanum, Huajuhong, Rhodiola, Turmeric, Chrysanthemum, Ephedra, Rose, Woody, Peilan, Peucedanum, Cinnamon, Black Medicine, Vinegar, Wild Chrysanthemum, Yizhiren, Chinese Rose Stir-fried husk with flowers, bran, sesame seeds, Andrographis paniculata, Cnidium monnieri, comfrey, etc. 

When decoction of Chinese medicine at home, in order to reduce the dosage, the decoction will be heated to evaporate a part of the water after the decoction is completed. 

The evaporation needs to be heated to 100 degrees C. High temperature will have an adverse effect on the quality of the medicine. We use low-temperature vacuum concentration. In a closed stainless steel tank, the Buddha point of the aqueous solution is reduced by vacuuming. 

At a lower temperature (40°C-60°C), the water will boil and evaporate. It has low evaporation temperature and fast evaporation speed. Prevent the active ingredients from being destroyed and decomposed by high temperature.