With so many drugs available, why do we need to test them instead of discarding them?

Some time ago, I wrote an article about the modernization of traditional Chinese medicine and why we need to test medicines, "How can innovative traditional Chinese medicine convince the public? Let's take a look at the scientific approach." Today I will continue to elaborate on this idea.

01. The misunderstanding of “a lot of medicines”

First of all, many people may have a misunderstanding, that is, " there are too many medicines ." Indeed, for many people, a cold seems to have dozens of brands or even more medicines to choose from, not to mention the various medicines in the pharmacy whose names are hard to pronounce, which gives us an illusion: there are too many medicines and we just need to make a choice.

In fact, this is a big misunderstanding about medicine.

Modern drugs are still insufficient in scale overall. Many drugs are modified or optimized based on past drugs. For example, the famous penicillin can be said to be the ancestor of antibiotics. It was first extracted from Penicillium by Fleming and found to have a very strong antibacterial effect. It successfully led mankind to the antibiotic era, turning many diseases from "incurable" into treatable diseases, especially during the World War, saving countless lives. However, natural penicillin also has some side effects, such as acid resistance, enzyme resistance and limited scope of application. In order to allow penicillin to treat more diseases and better serve mankind, scientists have made many modifications to penicillin, namely semi-synthetic penicillin and synthetic penicillin. These new penicillins can target more bacterial infections, have more ways of use, and play a greater role in treating diseases.

This way of transforming traditional drugs can be figuratively called "new flowers on old trees". Whether it is to reduce side effects, increase therapeutic effects or improve medication experience, it is the development of old drugs. However, they generally still belong to the penicillin class. If you want it to be antiviral, sorry, it's crossing the border.

Therefore, don’t think that we have many drugs to choose from. In clinical practice, you will find that in many cases, the range of choices is very small or even there is no targeted drug. For example, for the common cold, although you may think that there are many kinds of cold medicines and various brands make it difficult to choose. However, if you carefully read the instructions of various cold medicines, you will be surprised, because the ingredients of these cold medicines are basically the same.

For example, acetaminophen is often used to relieve fever and pain, ephedrine or pseudoephedrine is usually used to relieve nasal congestion, and antihistamines such as diphenhydramine and chlorpheniramine are used to treat sneezing and runny nose.

Many brands are just a combination of various ingredients, and the ingredients may even be exactly the same, so that after you carefully look at the ingredients of cold medicines several times, you realize that there are so few choices for cold medicines.

02. Why are there so few medicines?

One important reason why there are so few drugs is that drug development is very difficult.

Drug development requires a long cycle. First, we need to look for drugs in the laboratory. After finding them, we need to start various experiments, from cell experiments to animal model experiments. It is not enough to complete these. After all, the conditions in the laboratory are single, and animals and humans are not exactly the same. Therefore, drug development must undergo clinical trials. And this is a protracted research. Clinical phases 1, 2, and 3 require rigorous design and long trials, and most new drugs may fail at this stage. For example, many pharmaceutical giants have failed in the development of new drugs for Alzheimer's disease and suffered heavy losses.

Because of this, if effective drugs or relatively useful information can be found, it will be of great benefit to drug research and development, and traditional drugs can play this role.

03. Traditional medicine

When it comes to traditional prescriptions, many people may find them mysterious. However, if you think about it carefully, many traditional prescriptions are actually summaries of experience of medical practitioners. In the process of practicing medicine, they will summarize and record the treatment plans based on the theories or experiences they have learned.

Perhaps this process would be a little difficult for modern people to accept, for example, the views of relevant theories, such as the statistics of treatment effects that do not conform to the principles of modern statistics.

However, there is a very important point that should not be overlooked, that is: these drugs have been used before . In other words, compared with many drugs that are still in laboratory research and design, they have one more key content: clinical application.

You know, the ultimate purpose of drugs is to treat diseases in humans. In order to be rigorous and reliable, modern drug design requires laboratory trials before clinical research. The ancients did not have this condition, so they often skipped the previous part. Although this was risky and did not conform to modern scientific principles, they went directly to the clinic, and the clinic is the most core evidence and the gold standard for drugs.

Because of this, we can see that the medicines in these ancient books actually provide us with a basic directional content, which is actually very important for our modern medicines, because it can prevent us from taking many detours and become the basis for many of our research.

Today, drug verification based on ancient medical records and the search for new drugs has become one of the important areas of drug research and development.

04. How to conduct drug validation and development

Let's take a simple example to see how to conduct drug verification and development. In traditional medicine, there is a type of symptom called liver depression, blood deficiency and spleen weakness. This description can be said to be a very typical recording method in traditional medicine. From the perspective of modern medicine, how to interpret it?

1. Building a correspondence between traditional medicine and modern medicine

There are huge differences between the theories of Traditional Chinese Medicine and our modern scientific knowledge. Even the specific organ correspondences are often different. This is also a problem we often encounter when facing Traditional Chinese Medicine. The different systems make it difficult to understand.

Taking liver depression, blood deficiency and spleen weakness as an example, traditional medicine tends to give a descriptive explanation, liver depression, blood deficiency and spleen weakness. And traditional medicine explanations are proposed, such as "the liver fails to release qi, and qi is stagnant".

However, we can learn about the symptoms of this disease from traditional medicine. This disease often manifests itself in women as irregular menstruation, dysmenorrhea, breast pain, etc. This is much easier to understand. Moreover, this symptom still exists in modern people.

2. What are the treatment strategies for similar diseases in ancient books?

Now that we have done the symptom matching, let's take a look at how this symptom is treated in ancient books. In traditional medicine, there are treatment strategies such as Zhang Zhongjing's Sini San and Danggui Shaoyao San, which are drugs.

Don't underestimate this point. No matter how we ignore the records in ancient books, these medicines at least provide two important points for modern medicine.

1. The scope of application of the drug or the selection of treatment symptoms. The scope of application of the drug is a basic requirement. There are too many types of diseases, from head to toe and from inside to outside. If any drug does not tell the scope of application, it will be meaningless. After all, you can't try the drug for every disease. The description in the medical book can help us narrow the scope and know the disease that the drug targets, just like Sini San is targeted at liver depression and blood deficiency instead of joint pain, which determines its scope.

2. The idea of ​​testing the efficacy of the drug also came along. Modern medicine has targeted testing methods for diseases in these fields, which can better help us determine the basic ideas of testing and verification. Since Sini San and Danggui Shaoyao San are for irregular menstruation, dysmenorrhea, breast pain, etc., we can generally determine that this is closely related to hormone endocrine.

Having determined these two basic concepts, the next question is, is it really effective? Can it withstand the research of modern medicine?

05. Drug testing

The researchers combined Sini San and Danggui Shaoyao San to form Xiaoyao Mixture, and then used an experimental-control treatment on patients with irregular menstruation. They found that after the corresponding treatment, the users' irregular menstruation was significantly improved [1].

Further observations on common hormones in the menstrual process, such as estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), revealed that the hormone levels of the users were better improved before and after treatment.

It can be seen that Xiaoyao Mixture can improve irregular menstruation, which proves that the prescription recorded in the ancient book is an effective prescription and can be used to supplement the needs of modern medicines...

06. Know the reason behind it

Of course, according to modern scientific understanding of drugs, this is still not enough, because we should not only know its efficacy, but also further understand the mechanism by which the drug works.

So what is behind these drugs? Researchers have conducted phytochemical studies on these drugs. For example, white peony root is the basic ingredient, which is naturally very complex in chemistry.

The key chemical components of the root, Bupleurum chinense, were identified and 46 saponins, 8 flavonoids, 6 coumarins, and 6 enynes were found in the root. Other components included fatty acids, lignin, caffeic acid, chromones, sugar alcohols, etc. [2].

Among them, the content of common medicinal ingredients such as saponins and flavonoids is the highest, and these ingredients are generally believed to play an important role in regulating hormones, metabolism, etc.

Therefore, it can be roughly seen that ancient prescriptions such as Xiaoyao Heji are also tenable in terms of medicinal ingredients.

Of course, according to the thinking of modern pharmacy, the dosage form also needs to be improved. For example, traditional pills are taken directly from medicinal materials and can only be absorbed by the human body after digestion, while Xiaoyao Mixture and the like undergo a complete preparation process before the effective ingredients are dissolved, making them easier to absorb. At the same time, this extraction can reduce the intake of drug impurities and reduce the burden on the liver and kidneys. Of course, this extraction process is also an important achievement of modern pharmacy, such as fingerprint hormone identification of medicinal materials and optimization of extraction methods to ensure drug efficacy.

Of course, if further development is required, it will be necessary to obtain chemical monomers and conduct more rigorous modern medical verification on them.

In fact, if you are interested in looking at many units that conduct plant research, such as various botanical research institutes and plant-related colleges in agricultural and forestry colleges, you will find that interpreting the components of plants based on folk records and obtaining corresponding phytochemical components with therapeutic effects has become a basic research idea. This is also very meaningful for drug development and promoting the health of more people.

Finally, I have always adhered to a basic concept: drugs are used to treat diseases. Even to a certain extent, the "white cat, black cat" theory is feasible. After all, treating the disease is the first priority. Of course, on this basis, more rigorous demonstration of drugs can make the use of drugs more assured.

[1] You Zhiheng, Yu Qingqian. Clinical efficacy of Xiaoyao Pills combined with Siwu Decoction in the treatment of menstrual disorders of blood stasis and blood deficiency type[J]. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine, 2023, 33(12): 61-63.

[2] Bai Xue. Study on quality evaluation of Bupleurum chinense based on LC-MS metabolomics[D]. Shanxi University, 2023.