The TCM Model of Transnasal Drug Administration

The Old Book of Tang · Biographies of Arts and Techniques records: "Xu Yinzong was a native of Yixing, Changzhou. He initially served the Chen dynasty as an Outer Military Adjutant to the Prince of Xincai. At the time, the Dowager Consort Liu suffered from wind stroke and was unable to speak. Renowned physicians treated her to no avail; her pulse grew ever deeper and her jaw remained clenched shut. Yinzong said: 'Medicine cannot be administered by mouth. It should be given as a decoction whose vapor can fumigate her, allowing the medicinal properties to penetrate the interstices of the skin. Once the channels are thoroughly permeated, she will recover.' He then prepared dozens of hu of Astragalus and Saposhnikovia decoction and placed it beneath the bed. The vapor rose like smoke and mist, and that very night she was able to speak again. He was thereupon promoted beyond his rank to serve as Prefect of Yixing."

The New Book of Tang · Biography of Xu Yinzong also records this incident: "The Dowager Consort of the Prince fell ill with wind stroke and could not speak. Her pulse was deep and difficult to assess, and physicians declared their methods exhausted. Yinzong said: 'A liquid draught cannot be administered.' He then boiled dozens of hu of Astragalus and Saposhnikovia decoction and placed it beneath the bed. The vapor rose like mist and fumigated her. That evening, she spoke."

This is perhaps the earliest recorded instance in ancient Chinese texts of treating disease through transnasal drug administration in traditional Chinese medicine. The passage above recounts the story of how the Tang dynasty physician Xu Yinzong treated the Dowager Consort of the Prince of Xincai for stroke. The consort had suddenly suffered a stroke, her jaw was clenched shut, she was unconscious and unable to speak, and her condition was critical. Many physicians were summoned, but none could effect a cure.

After examining the patient, Xu Yinzong concluded that since she could not take medicine orally, an alternative approach was needed. He devised a method: he boiled Chinese medicinal herbs—Astragalus (Huangqi) and Saposhnikovia (Fangfeng)—into a decoction and placed it beneath the consort's bed. The medicinal vapor spread like smoke and mist throughout the room. Although the consort could not speak, she could still breathe. After inhaling the medicated vapor, it took effect, and that very night she regained consciousness and was able to speak.

This model of transnasal drug administration was likely already in limited circulation during the Tang dynasty. Sun Simiao, the celebrated Tang dynasty physician who was later honored by posterity as the "King of Medicine" and who was a contemporary of Xu Yinzong, also recorded several methods of transnasal drug administration in his work Prescriptions Worth a Thousand in Gold (Qianjin Fang). There are three passages in the Qianjin Fang that document this therapy.

"Spread a thin layer of prepared mugwort onto a piece of paper four cun wide. Then spread powdered sulfur evenly over the mugwort, ensuring it is uniformly distributed. Take a reed the length of the paper and roll the paper around it to make ten rolls. First, burn away the reed from the wrapped end, and inhale the smoke through the opening. Swallow the smoke to induce vomiting, then stop. The next morning, fumigate again as before, once or twice a day, until recovery occurs naturally. White rice porridge may be consumed; all else is to be avoided."

"Grind one liang of orpiment into a fine powder. Place it together with wax paper and mix the orpiment evenly into the paper. Roll it as in the previous method and fumigate in the same manner, once or twice a day, until vomiting is induced. After seven days of recuperation, supplement with mutton broth."

"Take a piece of worn green cloth four cun wide. Spread mugwort on the cloth, spread powdered green vitriol over the mugwort, spread a small amount of powdered orpiment over the vitriol, then a small amount of salt, and finally a small amount of powdered fermented soybean. Roll it tightly and set it alight. Place it in a dry jar, cover the head with paper, make a small opening, and inhale the smoke through it, swallowing it gently until vomiting is induced. If there is tightness in the chest, pause briefly until the smoke dissipates, then stop. Use once or twice daily; if three rolls are not fully consumed and recovery occurs, discontinue. Avoid greasy foods for twenty-one days."

Xu Yinzong was born in 536 AD and died in 626 AD, living to the age of 90. The exact birth and death years of Sun Simiao are unknown; he was likely born between 541 and 581 AD and died in 682 AD, living well past one hundred. The two men were essentially contemporaries, and both used or documented methods of transnasal drug administration. It is reasonable to infer that this method had already achieved a certain degree of popularity during the Tang dynasty.

My most direct impression of transnasal drug administration comes from my father. He learned from local folk practitioners a folk remedy for treating acute throat diseases, and it was remarkably effective. He would squeeze the juice from fresh Sedum lineare (stonecrop) and drip the juice into the nose to treat sore, swollen throats. The results were excellent—generally, throat swelling and pain would be relieved within half an hour of application.

I once pondered why our local folk practitioners administered medicine through the nose. For a time, I speculated it was because the stonecrop grown in our area was extremely bitter (and indeed it is very bitter—I tasted it myself). But upon deeper reflection, I realized there was another reason. Patients suffering from acute tonsillitis or acute pharyngitis experience such severe throat swelling that they cannot swallow even a drop of liquid, making transnasal administration the only viable route.

Whether it was renowned physicians like Xu Yinzong and Sun Simiao, or ordinary folk in our hometown, one can say they were all remarkably resourceful. In an era before modern intravenous infusion technology existed, when treating diseases that prevented normal oral medication, they devised many ingenious methods to deliver medicine into the body. It is evident that this method of transnasal drug administration was widely practiced among the people and has a long history.

I have previously written about the Song Family Fumigation-Inhalation Therapy, a unique treatment method developed by Dr. Song Shiqi, a contemporary Chinese physician (now deceased for many years). The Song Family Fumigation-Inhalation Therapy involves placing several specially processed, extracted, and refined Chinese medicinal herbs into a sealed metal container, where they are heated to a high temperature until they sublime into fine medicinal particles. The patient inhales these particles through the mouth and nose into the lungs, where they are absorbed by the pulmonary capillaries into the pulmonary venous blood, reach the heart, and are then distributed throughout the body to produce therapeutic effects.

Dr. Song Shiqi also published a monograph titled Song Family Fumigation-Inhalation Therapy to introduce his treatment method. Dr. Song primarily used this unique therapy to treat cancer, post-stroke sequelae, Parkinson's disease, and other conditions, with a certain degree of efficacy. Before his death, Dr. Song served as the deputy director of a hospital in Xingtai, Hebei Province. His innovative therapy was reported by the Guangming Daily in 1988, attracting widespread attention. However, because his method involved the use of highly toxic substances such as arsenic, it raised serious safety concerns and sparked considerable controversy, ultimately leading to a lawsuit between Dr. Song and a newspaper over alleged defamation.

I once wrote an article titled "The Anti-Cancer Principles of TCM Fumigation-Inhalation Therapy," which provided a detailed introduction to Dr. Song Shiqi's therapy. Unexpectedly, this article caught the attention of Dr. Song's family, and his nephew later contacted me.

Dr. Song's nephew now works at the Anguo Chinese Medicinal Materials Market in Hebei Province. He told me that Dr. Song's fumigation-inhalation therapy had been passed on to his two sons-in-law, but the elder son-in-law, Dr. Cang, has also passed away, and the younger son-in-law is now elderly and retired. As a result, this fumigation-inhalation therapy is essentially no longer practiced by anyone.

The most recent case of transnasal drug administration I encountered was an article I saw on Zhihu, in which a patient's family member shared how a Chinese medicinal pillow cured his wife's severe insomnia and mental disorder. This family member shared the formula for his calming and sleep-aiding medicinal pillow.

Formula: Caulis Polygoni Multiflori (Ye Jiao Teng) 350g (coarse granules), Semen Ziziphi Spinosae (Suan Zao Ren) 250g (coarse granules), Flos Albiziae (He Huan Hua) 150g (coarse granules), Radix Polygalae (Yuan Zhi) 120g (coarse granules), Semen Cassiae (Jue Ming Zi) 80g, Spica Prunellae (Xia Ku Cao) 30g (cut into small segments), Lavender 30g, Sandalwood 10g (coarse granules).

Anyone familiar with Chinese medicine can readily discern the therapeutic purpose of this formula. Flos Albiziae and Caulis Polygoni Multiflori constitute one of the most classic TCM herb pairs for calming the spirit and promoting sleep. The He Huan An Shen Tang (Albizia Calming Decoction) in the Yi Chun Sheng Yi for treating insomnia with excessive dreaming, and the Yang Xue Jie Yu Tang (Nourishing Blood and Resolving Stagnation Decoction) in the Fu Ke Yu Chi for treating postpartum depression, both primarily employ this herb pair in their formulations.

Semen Ziziphi Spinosae and Radix Polygalae are also among the most commonly used Chinese medicinal herbs for calming the spirit and aiding sleep. Semen Cassiae and Spica Prunellae have blood-pressure-lowering effects, among other functions. Lavender and sandalwood are aromatic substances that also have calming and sleep-promoting properties, and their inclusion in this herbal combination makes the fragrance more pleasant and acceptable.

Therefore, upon seeing this formula, I immediately judged it to be effective. I promptly prepared several such medicinal pillows for my family and friends, though I mixed the herbs with buckwheat hulls when making the pillows. Some of my relatives and friends who suffered from insomnia were the first to try them. After use, they all experienced excellent calming and sleep-promoting effects.

This led me to reflect: what exactly is the therapeutic mechanism at work here? I decided to try the pillow myself. Since I do not suffer from insomnia—I generally go to bed early and rise early, sleeping six to seven hours each night and taking about an hour's nap at midday, so my daily sleep is sufficient—the medicinal pillow did not have a significant effect on me. However, I was able to personally experience how the medicinal properties entered the body.

The faint medicinal fragrance emitted by the pillow drifted around the head throughout the night. Some of the small molecules of the medicinal compounds must have entered the nose through molecular diffusion and been inhaled into the body, making this yet another form of transnasal drug administration. Since the compounds enter the nasal cavity solely through molecular diffusion, only trace amounts of the active medicinal components are absorbed. However, the continuous transnasal administration throughout the night maintains a sustained therapeutic effect, which is why this method may actually produce longer-lasting results than taking oral sleeping pills.

The nasal cavity is richly supplied with capillaries and lymphatic capillaries, making transnasal drug administration conducive to rapid drug absorption. Modern medicine employs transnasal drug administration in vaccination and in the treatment of certain specific diseases—for example, influenza vaccines are administered as nasal sprays. Western medicine also uses transnasal drug delivery to treat other conditions, such as using esketamine nasal spray for treatment-resistant depression. Research is also underway to explore the use of intranasal peptide therapies, including insulin and oxytocin, for conditions such as Alzheimer's disease.

Transnasal drug administration holds certain advantages in the treatment of neurological and immunological diseases, and it merits deeper investigation. If we can develop safe and effective transnasally administered drugs for the treatment of cancer, neurological disorders, and immune system diseases, we could relieve the suffering of many patients. However, the safety of patients must always be given thorough consideration in the use of any therapeutic method or medication.

A Supplement to the Article "The TCM Model of Transnasal Drug Administration"

I previously wrote an article titled "The TCM Model of Transnasal Drug Administration." Recently, while studying a course in Western pharmacology, I gained some new insights, and I would now like to offer some supplementary remarks on that article.

Transnasal drug administration is a form of inhalation drug delivery. The nasal mucosa is richly vascularized with capillaries and can directly absorb drugs. After absorption through the nasal mucosa, the drug enters the systemic circulation directly and is distributed throughout the body via the arteries. This route of administration is subject to very little first-pass elimination.

Here, I would like to explain the concept of first-pass elimination. First-pass elimination, also known as first-pass metabolism or the first-pass effect, refers to the phenomenon whereby certain drugs, after oral administration, are metabolized by enzymes in the intestinal wall or the liver as they pass through, resulting in a reduction of the amount of active drug that reaches the systemic circulation and a corresponding decrease in therapeutic efficacy.

Thus, although oral administration is the most common and safest route of drug delivery, its efficacy is inevitably affected by the first-pass effect. Moreover, orally administered drugs must pass through multiple steps in the systemic circulation, resulting in a slower onset of action.

Transnasal drug administration is almost entirely unaffected by the first-pass effect, allowing the full therapeutic potential of the drug to be realized. Its onset of action is second only to intravenous administration, and it is faster than other common routes of administration, including sublingual, rectal, intramuscular, subcutaneous, oral, and transdermal delivery.

This provides a reasonable explanation for the rapid onset of efficacy observed in several of the treatment methods I mentioned in my article "The TCM Model of Transnasal Drug Administration," such as using Sedum lineare to treat sore, swollen throats and inhaling arsenic compounds to treat lung cancer.

This further underscores the considerable value of the TCM model of transnasal drug administration as a subject worthy of further research.