History of the Chinese Medicinal Gelatin : Chinese Medicine and Culture (2024)

1 Introduction

The Chinese term E Jiao (阿胶 Asini Corii Colla) refers to a medicinal gelatin extracted from donkey-hide in Dong’e county, Shandong Province, China. The finest gelatin is made by boiling the hide with water from the Ejing well. The “E” of E Jiao and the county name Dong’e derive from the term “Ejing” (“jing” is the Chinese term for “well”). Perhaps in Chinatowns in the western countries, Chinese turtle jelly is used more often than E Jiao, but E Jiao is quite a popular gift among the middle class. Although E Jiao has more than 2000 years of history in China, it is mentioned rarely in the West. Therefore, the aim of this article was to describe the history of the medicinal use of the animal glue (gelatin) in China (Figs. 1–3).

2 Cowhide glue

The term “jiao” (胶) widely refers to the glue (gelatin) consisting of collagen and other fiber proteins extracted by boiling hide from various animals, such as cows, horses, deer, and donkeys. The animal glue or gelatin is solid at room temperature, but dissolves at approximately 50 °C in hot water. Because of its useful properties, gelatin has been used as an adhesive for centuries in many parts of the world. Its use can be traced back as far as ancient Egypt, where it was used as an adhesive on burial accessories; cowhide glue was also used in colored wall paintings dating back 4400 years.¹ Brightly colored minerals, which generally do not dissolve in water, can be used as pigments if they are ground into powder and mixed with warmed glue. There are similar examples from ancient Greece and Rome, where people used cowhide glue. The glue was called κ ó λλα in Greek, which is the origin of the word “collagen.”² Similarly, in China, gelatin has been used to make mineral pigments and solid ink by mixing it with the soot of burned pine trees or other materials. The use of glue as an adhesive and pigment spreader is one of the most important ancient inventions.

In China, a vessel containing an adhesive made from cowhide gelatin was unearthed at the Xiaohe cemetery site (1980–1450 BCE), at the eastern end of the Tarim Basin.³ Gelatin seems to have been invented and first used in ancient Egypt and spread worldwide. This is because Chinese medicinal gelatin was initially made from cowhide, its processing method might have been introduced to China from the West through the Xinjiang region. At the very least, it is clear that cowhide glue was produced by mature manufacturing technology and widely used as an adhesive in prehistoric times.

In Chinese literature, the Chinese term “jiao” first appeared in the Shi Jing (《诗经》 Book of Odes), a collection of poetry complied before the 7th century BCE. The radical index of the character “jiao” is the moon and it represents a piece of marbled meat, suggesting that jiao is associated with animals. The Zhuang Zi (《庄子》) states that “Only when the ears of Gu Kuang (瞽旷 a famous blind musician) are plugged, people will appreciate their own ears … Only when the eyes of Li Zhu (离朱 an iconic figure with superhuman eyesight) are glued [jiao], people will believe their own eyes (（塞瞽旷之耳,而天下始人含其聪矣……胶离朱之目,而天下始人含其明矣）”)”⁴ (Chapter “Quqie” 胠箧). Here, the character “jiao” is a verb that means “sticking.” The use of “jiao” as a verb to describe sticking has a long history in China, indicating the widespread use of animal glue as an adhesive.

The Shui Hu Di Qin Mu Zhu Jian (《睡虎地秦墓竹简》 Qin-Period Bamboo Texts of Yunmeng) recorded officials used animal glue to repair ox carts. The section on statutes of public works (Sikong Lyu 司空律) stated that, “If your department has an abundant budget, you purchase glue by yourself.

If facing a small budget, you should claim fat and glue monthly and save them up … (to repair a cart) …. use one liang (—一两, ca. 16 g) of glue and two chui (二锤, ca. 10.7 g) of tallow. If a cart part is distorted and the glue comes off, apply glue to a thickness of a few fen (数分，, ca. 4–5 cm) （官有金钱者自为买脂胶，毋金钱者乃月为言脂胶，期。一脂攻间大车一两，用胶一两、脂二锤。攻间其扁解，以数分胶以之。)).”⁵ These bamboo slips revealed that glue was so expensive it could not be covered by miscellaneous expenses. The Kao Gong Ji (《考工记》 Records on the Examination of Craftsmanship), estimated to have been written in the Han dynasty, described in relative detail the varieties of glue and the processing method of making bows (Fig. 4).⁶

Animal gelatin in China was an important ingredient used in many processes before it was used for medicinal purposes.

3 Medicinal gelatin

The earliest record of medicinal gelatin is found in the silk-cloth text Wu Shi Er Bing Fang (《五十二病方》 Prescriptions for Fifty-two Diseases) (Fig. 5).⁷ Dated from the western Han dynasty, the scroll was excavated from the Ma Wang Dui tomb. Because the Wu Shi Er Bing Fang is considered to contain medical knowledge originating before the First Emperor of Qin (246–210 BCE), the medicinal use of gelatin can be traced further back to the Warring States period. Regrettably, there is little medical literature from the Warring States period and earlier; therefore, it is not possible to clarify when the use of medicinal gelatin began. In early China, medicinal gelatin was not extracted from the hide of the donkey. There were six origins of gelatin listed in the Records on the Examination of Craftsmanship: deer, horse, cow, rat, fish, and rhinoceros, but donkey had not been mentioned.⁶ At that time, donkey had just been introduced to the Yellow River plain, but gelatin was not widely extracted from donkey-hide because of the scarcity of donkeys.

There are two types of medicinal gelatin, namely E Jiao and Bai Jiao (白胶), listed in the Shen Nong Ben Cao Jing (《神农本草经》 Shennong's Classic of Materia Medica) (Fig. 6). The book is considered as being compiled circa first to second centuries ACE, and the gelatins are found under the high-class medicinal group. This herbal text does not mention any difference between the two types of gelatins and describes their tastes and properties as identical. Both types of gelatin are sweet (甘), have a neutral (中) medicinal property and possess similar medical benefits. This is the first time that the term “E Jiao” appears in Chinese literature. The “E” derives from the name of a place. Both E Jiao and Bai Jiao are used to prevent miscarriage and stabilize the condition of unborn babies and pregnant women. In addition, E Jiao can treat abnormal uterine bleeding whereas Bai Jiao can treat amenorrhea and infertility. Pregnant women are prone to anemia because blood is diverted to supply the fetus during pregnancy. Therefore, E Jiao is an appropriate medication to supplement blood during pregnancy (Fig. 7).

Blood coagulation involves the formation of fibrin clots that stop bleeding, create scabs, and repair wounds. This blood function may remind us of the above mentioned description of the cart been repaired with animal glue. It is natural that early societies associated animal glue with blood and regarded it as a substitute for blood. This may relate to the doctrine of signatures. The adhesive properties of gelatin, which help to make a structure stable and solid, may have been linked to stabilization of the fetus in the womb to prevent premature birth, treatment of abnormal uterine bleeding, and easing of blood flow. The Ming Yi Bie Lu (《名医别录》 Miscellaneous Records of Famous Physicians), which first defined E Jiao and Bai Jiao are made of cowhide and antlers, respectively, also stated that E Jiao is good for relieving fatigue and is suitable to treat people with weak limbs, probably because it was believed to have functions of reinforcement for muscles, bones, and tendons.

It is important to note that the medicinal use of animal gelatin is almost exclusive to China. Although a German scholar, Dr J. Liesegang, mentions the historical use of animal gelatin in ancient Egypt and Greece in his thesis The Gelatin in Medicine, there are no descriptions of its medical use in the West until the 19th century. The use of gelatin to facilitate the swallowing of medicine was invented by a French pharmacist, François Mothes, in the 19th century and is still in widespread use today.⁹ However, this application assumes that gelatin itselfhas no beneficial effect. In 1896, A. Dastre and N. Floresco gave dogs an intravenous injection of gelatin solution as a treatment to promote blood clotting without thrombo-sis.¹⁰ This is the earliest medicinal use of gelatin in the West.

Gelatin has been eaten for a long time in the West, although there are few records of its culinary use. Aspic, which is produced by boiling fish heads, was introduced as a high-class dish in a cookbook in Baghdad approximately 10th century.¹¹ The modern use of gelatin for desserts dated from the 18th century, when it became possible to mass production.

After all, the medicinal use of animal gelatin has not been known. It is almost exclusive to China, Japan, and other East Asian countries.

4 Water from the Ejing well

Miscellaneous Records ofFamous Physicians states that E Jiao was produced in Dong’e. The book states that E Jiao is named after Dong’e because it was produced there. Therefore, we can assume that the name E Jiao derives from the name of the region that produces it. Other herbal plants, such as Gao Liang Jiang (高良姜 Rhizoma Alpiniae Officinarum), Chuan Xiong (川芎 Rhizoma Ligustici Chuanxiong), and Wu Zhu Yu (吴茱萸 Fructus Evodiae), are also named after the regions where they are produced, but domesticated animals do not require specific conditions for breeding and can be kept almost anywhere. This raises the question of why medicinal gelatin was produced only in Dong’e. In the Shui Jing Zhu (《水经注》 Commentaries on the River Classic), Li Daoyuan, a geography expert, states that, “There is a big well on the west bank inside and near the north gate of the city. Its diameter is as long as a wheel (approx. 1.2 m); its depth is between 13.8 m and 16.2 m. Jiao was once used as a tribute to the imperial court. This is E Jiao described in the herbal texts. Therefore, people also called the well “Ejing” (Ejing was named after E of E Jiao).”¹²

E Jiao was produced much earlier than the sixth century. It has also been suggested that the well water was used in the E Jiao manufacturing process. In 657 ACE, the Tang emperor Gaozong ordered the official Su Jing and others to revise existing herbal texts and to conduct a large-scale nationwide survey of herbal drugs. However, the final report of this survey, Xin Xiu Ben Cao (《新修本草》 Newly Revised Materia Medica) did not mention the water of the Ejing well. In the supplemental work to the Newly Revised Materia Medica, Chen Cangqi clearly explained that the E Jiao production process required water from the Ejing well. He wrote in the Ben Cao Shi Yi (《本草拾遗》 Supplement to Materia Medica) that, “the gelatin is made by boiling it in water from the Ejing well. Most [gelatin] is a vulgar product that is counterfeit.”¹³ Chen Cangqi was particular about the variety of water; consequently, he listed another 35 varieties of water (including steam and hail) in addition to the Ejing water in the mineral drug section of his work. In the same period, Lu Yu, the Sage of Tea, discussed water sources in as much detail as the variety of tea leaves in his Cha Jing (《茶经》 Classic of Tea),¹⁴ and in the 9th century Zhang Youxin compiled the Jian Cha Shui Ji (《煎茶水记》 Record of Water for Tea).¹⁵

In the eighth and ninth centuries, Chinese intellectuals become more interested in water quality.

This concern for water sources and quality led to the depletion of water resources. In the 11th century, when Su Song and other officials conducted a nationwide survey of herbal medicines by imperial order, they described E Jiao as follows: “The genuine E Jiao is produced with the water from the well in the city Bai Cheng in E-Xian County. To produce it, boil black donkey skin with Ejing water, exactly following the original glue process. Because the well is officially prohibited, it is extremely difficult to obtain genuine E Jiao. Yet it is abundant in the imperial capital, namely Kaifeng (开封). However, these are probably not genuine products.” The text tells us that the Ejing water was officially controlled, and a large amount of E Jiao was made using other source of water. As described above, water quality is much more important than the quality of the donkey-hide. Li Shizhen also emphasized the importance of Ejing water, and added it as a new separate entry in his Ben Cao Gang Mu (《本草纲目》 Compendium of Materia Medica). He introduced the medical benefits of E Jiao, such as its anti-nausea properties and ability to increase the flow of phlegm. Furthermore, quoting from the Waterside (Shuidi 水地) chapter of the book Guan Zi (《管子》), he also introduced the medical theory that the character and constitution of the human body are affected by the nature of local water. He concluded that water from the Qi region strengthened the body and prevented skin diseases and hangovers.

Does the Ejing well water have any outstanding properties? A water inspection conducted by a local laboratory showed that Ejing water contains more minerals than water from other areas.¹⁶

5 Donkey-hide gelatin

E Jiao was probably not made from donkey-hide (as it is today) until the early Tang dynasty. Donkey-hide gelatin is not mentioned in the Newly Revised Materia Medica, but the book does mention a gelatin made from antlers called “ Bai Jiao.” However, Chen Cangqi makes a remark that, “ the donkey-hide gelatin is best for suppressing wind.” The 10th century Ri Hua Zi Ben Cao (《日华子本草》 Herbal of Rihua Zi) stated that, “Donkey, its skin is able to suppress all types of wind if you eat the boiled gelatin.”¹⁷ It was believed that donkey-hide gelatin could suppress any type of wind. The transition to donkey-hide gelatin for medicinal purposes is described in detail by Zhang Jinju et al.,¹⁸ Zhao Jiashen et al.,¹⁹ and other authors. This issue has been discussed in detail in these earlier papers, such as the supply of donkey-hide gelatin increased because the deteriorated quality of cowhide gelatin during the Northern Song dynasty (960–1127 ACE).

Li Shizhen mentioned that, “In general, gelatin is manufactured from the tenth to the second or third lunar months. Cowhide, water buffalo hide, and donkey-hide are superior, followed by hide from pigs, horses, mules, and camels … Early formulas included cowhide (gelatin) … Later, donkey-hide (gelatin) was praised.”²⁰ Li Shizhen's description makes it clear that the reputation of donkey-hide gelatin was growing since the Song dynasty.

6 Medicinal gelatin in Japan

Since ancient time, there have been few donkeys in Japan and almost no production of donkey-hide. However, medicinal gelatin was produced in Japan. According to the Engi Shiki (《延喜式》 Procedures of the Engi Era) in 927 ACE), Musashi Province (present Tokyo Prefecture and Saitama Prefecture) was obliged to give an annual tribute of approximately 30 kg of gelatin together with Ma Huang (麻黄 ephedra) and Ma Zi (麻子 hemp seeds). Although gelatin was listed with herbal medicines such as ephedra and hemp seeds, the amount of glue was much larger than the amounts of the other medicinal materials, probably because it was mainly used for industrial purposes. There is an ancient custom in Japan of abstaining from eating meat because of its “kegare” (秽 impurity); this custom was strengthened by the introduction of Buddhism to Japan. The Engi Shiki contains a code of avoiding attendance at any ceremony for 3 days after eating domesticated animals. Therefore, the production and consumption of medicinal gelatin is not popular in Japan. The use of imitation meat became popular in Japan, particularly from 13th to 15th centuries, when Zen Buddhism flourished. For example, the traditional Japanese confectionery “yokan” (羊羹 which is literally translated as mutton soup) has its origins in a specific meat dish from China. However, when the dish was introduced to Japan by Zen Buddhist monks, it became a vegetarian dish containing imitation meat. Yokan is made by mixing powdered adzuki beans, yam, sugar, flour, and arrowroot powder. The mixture is cut to resemble the shape of a sheep's liver and steamed until it solidifies. In the Edo period, agar weed was widely used to solidify food, including yokan. These cooking methods were developed as part of the custom of abstaining from eating meat.²¹ While animal meat dishes were avoided, fish dishes were not contraindicated. There were cases when the soup of boiled fish cooled down and hardened spontaneously. It is thought that such gelatin was sometimes eaten, but not for medicine.

Records from the 18th to 19th centuries show that Japan imported E Jiao from China.²² At approximately this time, Koho-ha (古方派 the Antiquity School) of medicine was gaining prominence in Japan. Accordingly, the demand for E Jiao increased because it was often used in formulas developed by Zhang Zhongjing, an important physician of the Antiquity School. Zhang Zhongjing uses several formulas that include E Jiao in the Shang Han Lun (《伤寒论》 Treatise on Cold Damage), such as Zhi Gan Cao Decoction (炙甘草汤) for Taiyang disease, Zhu Ling Decoction (猪苓汤) for Yangming disease and other disorders), and Huang Lian E Jiao Decoction (黄连阿胶汤) for Shaoyin disease. Additionally, Zhang Zhongjing's Jin Gui Yao Lüe (《金匮要略》 Synopsis of the Golden Chamber) introduced Wen Jing Decoction (温经汤) and Xiong Gui Jiao Ai Decoction (芎归胶艾汤) in the chapter “Fu Ren Ren Shen” (妇人妊娠 Diseases of Women and Pregnancy). These two formulas accurately reflect the effect of stabilizing the condition of pregnant women described in the Shennong's Classic of Materia Medica. Although these five formulas are often currently prescribed to patients in Japan, E Jiao is not registered in the Japanese Pharmacopoeia. For this reason, qualified gelatin (based on the above pharmacopeial standard) is sometimes used instead of E Jiao. In 1989, E Jiao was listed in the Japanese Standards for Non-pharmacopoeial Crude Drugs and it has been used in line with this standard ever since.²³ According to this standard, the raw material of gelatin is donkey-hide. In the Pharmacopoeia of the People's Republic of China, gelatin made from donkey-hide is called E Jiao, and gelatin made from cowhide is called Huang Ming Jiao (黄明胶). Water from the Ejing well is no longer required for the production of any of these types of gelatin.²⁴

The medical effect of E Jiao has also been studied in Japan. In a comparison of six formulas for kidney inflammation in rats, Zhu Ling Decoction showed the most effective anti-inflammatory activity.²⁵ The researchers focused on E Jiao because Zhu Ling Decoction had a better effect than Wu Ling Powder (五苓散), which does not contain E Jiao. However, they also realized E Jiao itself does not show anti-inflammatory activity. In addition, E Jiao-excluded Zhu Ling Decoction was not as effective as Zhu Ling Decoction. These findings show that E Jiao is essential to obtain an effect from Zhu Ling Decoction. Because E Jiao is an indigestible protein, its addition may slow the intestinal absorption of other ingredients. In other words, the auxiliary action of E Jiao may differ from that of gelatin capsules. If so, this explains the Lei Gong remark that “E Jiao fears Da Huang” as recorded in the Lei Gong Yao Dui (《雷公药对》 Leigong Drug Pairing).⁸ Purgative agents like Da Huang (大黄 Radix et Rhizoma Rhei) may not only reduce the effect of E Jiao, but may also reduce the effect of other herbal ingredients.

7 Conclusions

In China, animal gelatin has been used as an adhesive since prehistoric time. Descriptions of its medicinal use are found in the Wu Shi Er Bing Fang (《五十二病方》 Prescriptions for Fifty-two Diseases), indicating that it is one of the oldest TCM medicines. However, it is likely that its raw material was cowhide; therefore, it differed from modern medicinal gelatin. The name E Jiao first appears in the Eastern Han dynasty text Shennong's Classic of Materia Medica, and the ingredient is described as useful for symptoms related to pregnancy and menstruation. Zhang Zhongjing often used E Jiao in his formulas, most of which are still prescribed to patients today. However, Zhang Zhongjing's original formulas presumably contained E Jiao made from cowhide. In the Tang dynasty, E Jiao began to be produced from donkey-hide. During the Song dynasty, some physicians expressed a preference for donkey-hide gelatin over cowhide gelatin. Currently, gelatin made from donkey-hide is called E Jiao and gelatin made from cowhide is called Huang Ming Jiao in the People's Republic of China.

Japan has actively introduced Chinese medicine. However, since the consumption of animal flesh had been forbidden, the use of animal gelatin for medicinal purposes was shunned. When the Koho-ha school became mainstream in the late Edo period, physicians tended to prescribe E Jiao more often to patients because they placed an enormous emphasis on Zhang Zhongjing's formulars. As a result, Japan imported E Jiao from China.

From a historical perspective, cowhide gelatin should be used as E Jiao to authentically reproduce Zhang Zhongj-ing's formulas. Although there is a certain value in reproducing such ancient formulas, they are not always the best treatments for modern practice. The quality and healing properties of herbal medicines may change over time. Additionally, differences in the constitutions of people between ancient and modern times (owing to changes in food and drink customs) may alter the suitability of some herbal medicines by the change of the common diseases and symptoms. An example is the change from cowhide to donkey-hide as the raw material of E Jiao. To determine whether donkey-hide gelatin or cowhide gelatin is more effective in Zhang Zhongjing's formulas requires controlled experiments.

Funding

This study was financed by a grant from the Zhejiang Gongshang University, the Zhejiang Province “Foreign Language and Literature” Top Disciplines (A Class) Construction High-level Project (No. 2020YLZS16).

Ethical approval

This study does not contain any studies with human or animal subjects performed by any of the authors.

Author contributions

Teruyuki Kubo participated in manuscript review and writing. Teruyuki Kubo and Zhong-Zhen Zhao have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

Conflicts of interest

Zhong-Zhen Zhao is an Editorial Board member of Chinese Medicine and Culture. The article was subject to the journal's standard procedures, with peer review handled independently of Zhong-Zhen Zhao and his research groups.

References