Foreword

Over the past two decades, the range of active ingredients that can be loaded into Oral Dissolving Films (ODF) has expanded continuously—from early small-molecule chemical drugs to amino acid-based nutrients, and now to botanical extracts. This ever-improving carrier capacity has opened new technological pathways for sleep aid products.

Meanwhile, sleep-promoting ingredients themselves have undergone significant upgrades: from exogenous hormone supplementation, to endogenous neurotransmitter regulation, and then to multi-pathway synergistic natural botanical extracts. Each stage of evolution reflects the market’s growing demand for “more natural, safer, and more effective” sleep solutions.

This article systematically reviews the technical characteristics and market status of major existing sleep-promoting ingredients, with particular emphasis on the strategic value of the medicine-food homology direction represented by Sour Jujube Seed (Suanzaoren).

I. Overview of the Oral Dissolving Film Dosage Form

Oral Dissolving Film (ODF) is a subcategory of film preparations. The 1985 edition of the Chinese Pharmacopoeia formally included film preparations. In 2001, Pfizer’s Listerine launched breath-freshening ODF products, which were selected as one of Time magazine’s Best Inventions of the Year in 2002, marking the extension of ODF from pharmaceutical to consumer product applications. Between 2003 and 2007, more than 50 ODF consumer and OTC products were launched in North American and European markets.

Today, ODF technology has evolved into a versatile delivery platform, with applications ranging from pharmaceuticals and nutraceuticals to personal care products. Its key attributes—rapid disintegration, precise dosing, and convenient administration—have made it particularly well-suited for sleep aid applications, where rapid onset of action is highly desirable.

II. Melatonin

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone secreted by the pineal gland, playing a central role in regulating the circadian rhythm. As a sleep aid ingredient, melatonin entered the market in the 1990s and has since become one of the most widely used sleep supplements globally.

Mechanism of Action

Melatonin operates primarily through the MT1 and MT2 receptor pathways. Activation of these receptors promotes the onset of sleepiness and helps synchronize the body’s internal clock with the external light-dark cycle. However, its effects are largely limited to circadian rhythm regulation rather than direct sedation, meaning it is more effective for jet lag and shift-work-related sleep disruption than for chronic insomnia.

Development History in ODF

The first melatonin ODF products emerged in the U.S. market around 2010, leveraging ODF’s rapid disintegration advantage to deliver melatonin directly through the oral mucosa for faster absorption compared to traditional tablets or capsules. By 2020, melatonin-based ODF products had become a significant category in the U.S. sleep aid market.

Safety and Regulatory Status

In the United States, melatonin is classified as a dietary supplement and is available over-the-counter. In China, however, melatonin is not listed as a food raw material, meaning melatonin-containing products cannot be sold through regular domestic retail channels and are restricted to cross-border e-commerce only. Furthermore, long-term melatonin supplementation has raised concerns regarding potential endocrine disruption and hormonal imbalance, leading to increasing consumer skepticism about its safety profile.

Market Limitations

• Regulatory restriction: Not permitted as a food ingredient in China

• Safety concerns: Public debate over potential hormonal effects

• Limited efficacy: Primarily addresses circadian rhythm disruption, not broad-spectrum insomnia

III. Amino Acid-Class Sleep Ingredients

Following melatonin, amino acid-derived sleep ingredients gained attention for their ability to modulate neurotransmitter systems involved in sleep regulation. Key players in this category include GABA, L-Theanine, 5-HTP, and L-Tryptophan.

GABA (Gamma-Aminobutyric Acid)

GABA is the primary inhibitory neurotransmitter in the central nervous system. It works by reducing neuronal excitability throughout the nervous system, thereby promoting relaxation and sleep. In ODF formulations, GABA can be rapidly absorbed through the oral mucosa, bypassing first-pass metabolism. However, the blood-brain barrier penetration of orally administered GABA remains a subject of scientific debate, with some studies questioning its bioavailability when taken orally.

L-Theanine

L-Theanine, an amino acid found naturally in tea leaves (Camellia sinensis), promotes relaxation without causing drowsiness. It is believed to modulate alpha brain wave activity and increase GABA, serotonin, and dopamine levels in the brain. As an ODF ingredient, L-Theanine is well-tolerated and has a favorable safety profile, though its sleep-promoting effects are primarily anxiolytic rather than directly hypnotic.

5-HTP (5-Hydroxytryptophan)

5-HTP is a direct precursor to serotonin, which in turn can be converted to melatonin. It is commercially produced from the seeds of Griffonia simplicifolia, an African plant. While 5-HTP shows promise as a sleep aid, its regulatory status varies significantly across jurisdictions. In China, it is classified as a novel food ingredient or food additive with limited permitted applications, restricting its use in ODF products.

L-Tryptophan

L-Tryptophan is an essential amino acid that serves as the precursor to both serotonin and melatonin through the 5-HTP intermediate pathway. It has the longest history of use among amino acid sleep aids and is classified as a health food ingredient in China. However, its efficacy depends on successful conversion through multiple enzymatic steps, and the dosage required for meaningful sleep effects is relatively high, presenting challenges for ODF loading capacity.

Limitations of Amino Acid-Class Ingredients

• Single-pathway mechanism compared to botanical extracts

• Not classified as medicine-food homology ingredients in China

• Bioavailability concerns (especially for GABA)

• High loading requirements challenge ODF capacity constraints

IV. International Botanical Sleep Ingredients

Beyond amino acids, several botanical ingredients have gained prominence in the global sleep aid market, particularly in the United States and European Union. These include Acanthopanax senticosus (Eleuthero/Siberian Ginseng), Valeriana officinalis (Valerian), Chamomilla recutita (Chamomile), Passiflora incarnata (Passionflower), and Humulus lupulus (Hops).

Eleuthero (Acanthopanax senticosus / Siberian Ginseng)

Eleuthero has been used in traditional Chinese medicine for centuries as an adaptogenic herb. Its sleep-promoting effects are attributed to eleutherosides and polysaccharides, which modulate the hypothalamic-pituitary-adrenal (HPA) axis and reduce stress-induced cortisol elevation. However, Eleuthero is not included in China’s medicine-food homology catalog, creating regulatory barriers for food-grade ODF products.

Valerian (Valeriana officinalis)

Valerian root has been used as a mild sedative and sleep aid for over 2,000 years in European herbal medicine. Its active compounds, including valerenic acid, interact with GABA receptors to promote sedation. In the EU, valerian is a well-established herbal remedy with significant market presence. In China, however, it faces regulatory classification challenges similar to Eleuthero, limiting its application in food-grade products.

Chamomile, Passionflower, and Hops

These three botanicals are commonly used in Western sleep formulations. Chamomile contains apigenin, which binds to benzodiazepine receptors; Passionflower increases GABA levels; and Hops contributes bitter acids with sedative properties. While widely accepted in international markets, their regulatory status in China remains ambiguous, restricting domestic ODF product development.

Common Challenges

• High regulatory barriers in China for international botanicals

• Not included in China’s medicine-food homology catalog

• Limited clinical evidence for ODF-specific formulations

• Cross-border e-commerce dependency restricts market access

V. Sour Jujube Seed (Suanzaoren) — A Medicine-Food Homology Ingredient

Among all sleep-promoting ingredients, Sour Jujube Seed (Ziziphus jujuba var. spinosa seed, known as Suanzaoren in Chinese) occupies a unique position due to its classification as a medicine-food homology ingredient in China, granting it unparalleled regulatory flexibility for food-grade product development.

Historical Background

Suanzaoren has been used as a sleep aid for nearly 2,000 years in Chinese medical practice. It was first documented in the Shennong Ben Cao Jing (Divine Farmer’s Materia Medica), where it was classified as an upper-grade herb. Its traditional indications include calming the mind (Anshen), nourishing the heart, and promoting restful sleep. This extensive historical usage provides a robust foundation for modern product development and brand storytelling.

Active Compounds and Mechanisms

Modern pharmacological research has identified several key active compounds in Suanzaoren that contribute to its sleep-promoting effects:

• Jujuboside A and Jujuboside B: Saponin compounds that modulate GABAergic neurotransmission and prolong slow-wave (deep) sleep duration

• Spinosin: A flavone C-glycoside that acts as a partial agonist at 5-HT1A serotonin receptors, contributing to anxiolytic effects

• Betulinic acid: A pentacyclic triterpenoid with anti-inflammatory and neuroprotective properties

• Flavonoids and Alkaloids: A diverse group of compounds that contribute to multi-pathway sleep regulation through antioxidant, anti-anxiety, and sedative mechanisms

The multi-pathway mechanism of Suanzaoren represents a significant advantage over single-mechanism ingredients like melatonin (circadian regulation only) or amino acids (GABAergic pathway only). By simultaneously modulating GABA, serotonin, and inflammatory pathways, Suanzaoren addresses a broader spectrum of sleep disruption causes.

Medicine-Food Homology Status

Suanzaoren is officially listed in China’s medicine-food homology catalog, meaning it can be used as a raw material for ordinary food products without the regulatory restrictions that apply to pharmaceutical or health food products. This classification allows for: (1) distribution through all retail channels, including online and offline; (2) no requirement for health food (Blue Hat) certification; (3) direct consumer accessibility without prescription or cross-border e-commerce constraints.

Comparative Analysis with Other Sleep Ingredients

In summary, Suanzaoren possesses a triple advantage of “multi-pathway synergistic action, medicine-food homology regulatory status, and nearly two millennia of traditional use history.” Compared to existing ingredients, melatonin carries safety controversy and regulatory restrictions; amino acid-class ingredients have single-pathway mechanisms and are not classified as medicine-food homology; Eleuthero and Valerian face higher regulatory barriers. Suanzaoren is currently one of the few sleep-promoting ingredients that simultaneously satisfies the criteria of efficacy, safety, regulatory clearance, and market gap.

Product R&D Progress

Recently, domestic enterprises have initiated R&D exploration applying Suanzaoren extract to the ODF dosage form. For instance, Wuhan Jinglong Biotechnology Co., Ltd. has conducted technical research in the integration of Suanzaoren extract with ODF film-forming technology, though the technical feasibility of this direction remains to be validated by further clinical data.

Wuhan Jinglong Biotechnology Co., Ltd. has completed the R&D and internal validation of Suanzaoren ODF:

• Taste Performance: Natural flavoring technology effectively masks the bitterness of botanical extracts. The ODF has a smooth, refined mouthfeel and disintegrates rapidly

• Onset Characteristics: When taken before bedtime, users report feeling increased drowsiness within approximately 15 minutes

• Sleep Improvement: Reduced time to sleep onset, decreased number of nighttime awakenings, improved next-day mental state, and a trend toward extended deep sleep duration

• Safety: No adverse reactions reported by any trial participants, no next-day residual drowsiness, and no tendency for dependence (above findings are from small-scale internal trials and are for reference only)

Compound ODF: The Future Development Direction

Single-ingredient Suanzaoren ODF solves the “from 0 to 1” challenge of combining medicine-food homology with the ODF delivery system. The next step is “from 1 to N”: using Suanzaoren as the core ingredient and combining it with other medicine-food homology ingredients to build a compound ODF product line targeting different types of sleep disorders.

The medicine-food homology catalog provides abundant formulating possibilities. Lily bulb (Baihe, documented in the Shennong Ben Cao Jing as an upper-grade herb) moistens the lungs, clears the heart, and calms the spirit; Longan aril (Guiyuanrou) tonifies the heart and spleen, benefiting qi and blood, and is suitable for insomnia caused by excessive mental strain; Poria (Fuling) strengthens the spleen and calms the heart, showing significant efficacy for sleep difficulties caused by spleen and stomach weakness. All of these ingredients are included in the medicine-food homology catalog and can be used as ordinary food raw materials without additional regulatory hurdles.

At the same time, compound formulations combining modern nutritional ingredients (GABA, L-Theanine, Valerian extract, Chamomile extract) with traditional botanical ingredients have become a trend in international sleep products. As domestic raw materials are progressively incorporated into the food ingredient catalog or classified as novel food ingredients, their combination with ODF technology will open broader product possibilities—targeting different insomnia types such as circadian disruption, anxiety-driven, and stress-related, achieving multi-pathway synergistic regulation through scientifically optimized formulations.

The ODF dosage form possesses unique advantages in compound scenarios: multiple ingredients can be uniformly distributed within a single film, and a single application delivers multiple active ingredients simultaneously with consistent taste and precise dosing—significantly superior to traditional multi-pill regimens with tablets or capsules.

VI. Market Opportunity

The current domestic e-commerce sleep ODF market exhibits the following characteristics: products are predominantly melatonin-based formulations, imported brands dominate the market, and sales channels rely heavily on cross-border e-commerce. The “sleep ODF” category as an independent consumer product segment remains in the market cultivation phase.

Suanzaoren ODF is currently in a strategic window period characterized by product readiness, regulatory clearance, and market gap.

Core Differentiation Advantages:

• Natural Positioning: Medicine-food homology status differentiates it from melatonin’s “hormone” label

• Universal Channel Access: General food classification means no restriction to cross-border e-commerce channels

• Deep Sleep Enhancement: Extends slow-wave sleep, aligning with the consumer trend shift from “getting to sleep” to “getting quality sleep”

• Cultural Heritage: Nearly two millennia of calming tradition provides a natural foundation for brand narrative

• Product Scalability: Multiple compound SKUs can be derived from the core Suanzaoren formulation to cover different insomnia types

Conclusion

The continuous expansion of ODF carrier capacity has provided the technological foundation for deploying higher-quality sleep-promoting ingredients. The evolution of sleep ingredients—from hormone supplementation to neurotransmitter regulation, and onward to multi-pathway synergistic natural botanical extracts—reflects the market’s relentless pursuit of safe and effective sleep solutions.

As one of the sleep-promoting ingredients with the longest history of use in China, Suanzaoren has accumulated rich empirical and cognitive foundations through nearly two millennia of clinical practice. Wuhan Jinglong Biotechnology Co., Ltd. has completed the R&D and internal validation of Suanzaoren ODF, combining traditional medicine-food homology wisdom with modern ODF formulation technology.

Looking ahead, as food raw material policies gradually open, more natural sleep-promoting ingredients will be incorporated into the general food category. At that point, the sleep ODF product category will no longer be limited to single formulations, but will evolve into a diversified product matrix covering different insomnia types and demographic needs—from medicine-food homology compounds to modern nutritional combinations, the ODF delivery platform will carry an increasingly rich portfolio of sleep solutions, becoming an important component of the sleep health landscape.