**1. Introduction**

China, as a major tobacco producer, accounts for about half of the world's tobacco production. For tobacco, most of it will be used to produce cigarettes, while about a quarter of the leftover material will be discarded and not reasonably utilized [1]. For this part of tobacco waste, if discarded casually, it may destroy the structure of the soil on the one hand; on the other hand, the harmful components in the tobacco waste will also infiltrate into the groundwater, thus further harming human life [2]. In view of this, if these tobacco wastes can be reasonably used as resources, not only can the above problems be solved, but also a large number of natural chemical raw materials can be obtained, and the income of tobacco farmers can also be increased. In addition to this, it is also in line with China's policy on the resourcefulness of solid waste.

Numerous studies have demonstrated that tobacco leaves contain a number of active substances, such as saccharides, organic acids, alkaloids and proteins [3–7]. However, there are few studies on the contents of these substances in waste materials, such as tobacco stems [8]. Among many bioactive substances, chlorogenic acid has been widely used in the fields of medicine, food and cosmetics because of its good antibacterial, anti-inflammatory, free radical scavenging and anti-cancer properties [9–11]. At present, the extraction of chlorogenic acid in the literature was mainly derived from Chinese herbal medicines, such

**Citation:** Zeng, G.; Ran, Y.; Huang, X.; Li, Y.; Zhang, M.; Ding, H.; Ma, Y.; Ma, H.; Jin, L.; Sun, D. Optimization of Ultrasonic-Assisted Extraction of Chlorogenic Acid from Tobacco Waste. *Int. J. Environ. Res. Public Health* **2022**, *19*, 1555. https:// doi.org/10.3390/ijerph19031555

Academic Editor: Roberto Alonso González-Lezcano

Received: 28 December 2021 Accepted: 27 January 2022 Published: 29 January 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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as honeysuckle, *Eucommia ulmoides* leaves and so on [12–14]. Besides, most of them were extracted directly without any preprocessing. The extraction methods of chlorogenic acid mainly involve water extraction [12], alcohol extraction [14], ultrasonic extraction [15] and microwave extraction [16]. Among these methods, ultrasonic extraction of chlorogenic acid has the advantages of a fast mass transfer process and high extraction efficiency, which has attracted the attention of many researchers [17].

In order to further improve the resource utilization of tobacco waste and provide a reference for the extraction of chlorogenic acid from tobacco stems and other wastes. In the present study, chlorogenic acid was extracted from tobacco stems using double freeze-thaw method ultrasonic technology for the first time. The tobacco waste was first repeated freezing and thawing, and then the effect of ultrasonic time, temperature and ethanol content on the yield of chlorogenic acid was investigated using a single factor method. Finally, the response surface methodology (RSM) was used to find the optimal extraction process parameters.
