Traditional Chinese medicine extract chewing gum for assisting smoking cessation as well as preparation method and application of traditional Chinese medicine extract chewing gum

Abstract

The invention discloses traditional Chinese medicine extract chewing gum for assisting smoking cessation, a preparation method and application, and belongs to the technical field of assisting smoking cessation. The chewing gum consists of 10 medicinal and edible traditional Chinese medicine extracts and auxiliary materials, and the traditional Chinese medicine extracts are compatible according to'monarch, minister, assistant and guide 'and are designed aiming at the pathogenesis of'stagnation of lung due to smoke toxicity, lung dryness and spleen deficiency'. During preparation, the traditional Chinese medicines are soaked in a dark place at 25 DEG C, concentrated at low temperature and freeze-dried in vacuum to obtain the extract, and then the extract is mixed with the heated and softened edible gum base and the aromatic, molded and aged to obtain a finished product. The traditional Chinese medicine composition has physiological smoking cessation and psychological substitution effects, and the traditional Chinese medicines can clear smoke toxin, moisten lung and spleen and relieve withdrawal symptoms; the chewing action simulates smoking, and psychological dependence is relieved; and the gum base realizes drug sustained release and has a lasting effect. The product is safe, good in taste, capable of reducing relapse rate and suitable for assisting in smoking cessation.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chewing gum, and specifically provides a traditional Chinese medicine extract chewing gum for assisting in smoking cessation, a preparation method and application. BACKGROUND

[0004] The core difficulty of tobacco dependence lies in the withdrawal syndrome occurring during the process of smoking cessation, which specifically includes somatic symptoms, cognitive impairment and emotional disorders. These symptoms are key factors leading to high relapse rate after smoking cessation. Although a smoke-free environment can reduce the harm of second-hand smoke to a certain extent and assist in motivating smoking cessation, it cannot fundamentally solve the physiological and psychological dependence problems of smokers themselves.

[0005] At present, the technical solutions for intervening tobacco dependence at home and abroad mainly fall into four categories: first, nicotine replacement therapy, which alleviates withdrawal symptoms by supplementing low-dose nicotine, but has the risk of secondary dependence and cannot eliminate the body's nicotine; second, partial agonists of nicotine receptors, which play a role by blocking the binding of nicotine to receptors, but have high costs and can easily cause side effects such as nausea, dizziness and emotional abnormalities; third, antidepressants, which alleviate smoking anxiety by regulating neurotransmitters, but have limited applicability and can exacerbate the mental symptoms of some patients; fourth, non-drug therapy, which has highly dependent on individual compliance and unstable overall efficacy.

[0006] In addition to the above chemical and non-drug methods, there are also a small number of patents related to smoking cessation compositions in the prior art, such as patent number CN115814002A "a smoking cessation composition and a preparation method thereof". This scheme uses coffee bean extract, agastache extract, raspberry tea extract, etc. as raw materials and adopts a tabletting process to prepare a tablet or a tablet. However, such tablet formulations have significant defects: first, the oral swallowing use mode lacks the chewing experience and cannot simulate the oral movements during smoking, having weak psychological dependence relieving effect on smokers; second, the drug release speed of the tablet is slow and uncontrollable, making it difficult to quickly respond to the immediate needs of the onset of nicotine craving; third, the formula design does not consider the lung and spleen damage caused by smoking, and can only temporarily suppress nicotine craving through a single component, without the synergistic effect of "clearing nicotine and regulating viscera", and without taste or chewing durability design, which cannot transfer psychological dependence through long-term oral activity, and the overall smoking cessation effect is limited.

[0007] In addition, ordinary chewing gum products have chewing experience, but they have no active ingredients for smoking cessation and can only freshen breath, and cannot relieve physiological withdrawal symptoms, let alone assist in achieving long-term smoking cessation goals. In summary, the existing technology has obvious shortcomings in "safety, efficacy stability, and psychological replacement effect", and there is an urgent need for a new smoking cessation assistance technology that takes into account physiological smoking cessation, psychological replacement, and safety without side effects. SUMMARY

[0008] In view of this, the purpose of the present application is to overcome the defects of "obvious side effects, weak psychological substitution, and limited curative effect" in the existing auxiliary smoking cessation technology, and provide a traditional Chinese medicine extract chewing gum for assisting smoking cessation. The chewing gum takes traditional Chinese medicine extract with the same medicinal and edible properties as the active ingredient, combines the advantages of chewing gum dosage form, and realizes the dual effects of "physiological conditioning + psychological substitution" for smoking cessation.

[0009] The technical solution of the present application is as follows: the present application provides a traditional Chinese medicine extract chewing gum for assisting smoking cessation, which is composed of active ingredients and auxiliary materials. According to a mass ratio of 100%, the mass ratio and selection of each component are as follows: The active ingredients are composed of extracts of 10 traditional Chinese medicines with the same medicinal and edible properties. The traditional Chinese medicine compatibility logic of "jun, chen, zhu and shi" is adopted to achieve the synergistic effect of "clearing smoke toxin, moistening lung and spleen, and regulating viscera" for the pathogenesis of "smoke toxin stagnating in lung and lung dryness and spleen deficiency" caused by smoking. The mass ratio and efficacy of each extract are as follows: Ophiopogon japonicus extract: mass ratio 4.5-18%, with the effects of nourishing yin and moistening lung, benefiting stomach and generating saliva, and clearing heart and relieving restlessness, which can relieve dry cough, dry mouth and throat, and restlessness during smoking cessation caused by smoking; Glycyrrhiza uralensis extract: mass ratio 0.6-2.4%, with the effects of tonifying spleen and replenishing qi, clearing heat and detoxifying, relieving cough and expectorating phlegm, relieving pain and regulating the properties of various drugs, which can relieve sore throat and regulate the properties of other traditional Chinese medicine ingredients; Pericarpium citri reticulatae extract: mass ratio 1.875-7.5%, with the effects of regulating qi and invigorating spleen, drying dampness and resolving phlegm, which can improve the symptoms of sputum and spleen deficiency caused by smoking; Poria cocos extract: mass ratio 1.875-7.5%, with the effects of promoting water and removing dampness, invigorating spleen and calming heart, which can enhance the function of spleen and stomach, prevent "lung disease affecting spleen", and relieve anxiety during smoking cessation; Platycodon grandiflorum extract: mass ratio 1.245-4.98%, with the effects of promoting lung, resolving phlegm, benefiting throat and draining pus, which can dredge lung qi and relieve the feeling of foreign body in throat caused by smoking; Houttuynia cordata extract: mass ratio 1.875-7.5%, with the effects of clearing heat and detoxifying, resolving abscess and draining pus, and diuresis and relieving stranguria, which can clear smoke toxin in the lung and relieve lung heat and phlegm; Honeysuckle extract: mass ratio 1.245-4.98%, with the effects of clearing heat and detoxifying, and dispersing wind-heat, which, as the core ingredient of the monarch drug, can enhance the effects of clearing smoke toxin and anti-inflammatory; Momordica grosvenori extract: mass ratio 1.245-4.98%, with the effects of clearing heat and moistening lung, benefiting throat and opening voice, and smoothing intestine and defecating, which, as the minister drug, can assist Ophiopogon japonicus in moistening lung and improve the taste of chewing gum; Mint extract: 1.245-4.98% by mass, with the effects of dispersing wind-heat, clearing the head, benefiting the throat, and removing measles, and soothing the liver and promoting qi, as a medicinal herb, it can quickly relieve sore throat, at the same time, it can bring a cool taste and improve the use compliance; Phyllanthus emblica extract: 1.245-4.98% by mass, with the effects of clearing heat and benefiting the throat, moistening the lungs and reducing phlegm, and generating saliva to stop thirst, as a ministerial herb, it can assist Ophiopogon japonicus and Siraitia grosvenorii to enhance the effects of moistening the lungs and generating saliva.

[0010] The above-mentioned 10 kinds of traditional Chinese medicine extracts are all food and medicine categories, meet the requirements of the "National Food Safety Standard Food Raw Material Directory", have no side effects of chemical drugs, are high in safety, and are suitable for long-term use.

[0011] The auxiliary materials include edible gum base and flavoring agent, which work together to realize the functions of "chewing resistance, drug slow release, and taste optimization" of the chewing gum: Edible gum base: 31.6-82.45% by mass, selected from one or more of natural gum, synthetic rubber, and resin; wherein the natural gum includes sugar gum, xanthan gum, and balata gum, the synthetic rubber includes styrene-butadiene rubber, butyl rubber, and polyisobutylene, and the resin includes glyceryl ester of rosin, glyceryl ester of wood rosin, and polymeric glyceryl ester of rosin; the edible gum base has the effects of giving the chewing gum the physical property of chewing resistance, and serving as a drug carrier to realize the slow release of active ingredients and prolong the drug action time (more than 30 minutes); Flavoring agent: 0.4-0.8% by mass, selected from one or more of strawberry flavor, cherry flavor, mint flavor, menthol, vanilla flavor, and orange flavor; the flavoring agent has the effects of masking the slight bitterness of the traditional Chinese medicine extract, optimizing the taste, and improving the acceptance of smokers.

[0012] Another object of the present application is to provide a preparation method of the above-mentioned traditional Chinese medicine extract chewing gum, through specific low-temperature extraction process and molding process, the active ingredients of traditional Chinese medicine are maximized, and the product efficacy and taste are ensured.

[0013] In some embodiments, the preparation method includes four core steps of traditional Chinese medicine extract preparation, active ingredient mixing, chewing gum base preparation, molding and aging, which are as follows: The preparation of the traditional Chinese medicine extract adopts the "low-temperature preservation" process to ensure that the heat-sensitive active ingredients (such as mint volatile oil and honeysuckle chlorogenic acid) in traditional Chinese medicine are not destroyed, and the specific steps are as follows: 1. Immersion extraction: take single traditional Chinese medicine raw material (such as Ophiopogon japonicus and licorice), mix with pure water at a ratio of 1:10 (w / v), seal and place in a 25℃ environment for 72 hours of immersion extraction, stir every 12 hours during the period to ensure that the effective ingredients are fully dissolved; 2. Purification treatment: after the extraction is completed, the extract is placed in a centrifuge and centrifuged at a speed of 8000 rpm for 15 minutes to remove the residue of the raw material; then the supernatant after centrifugation is filtered by using a 0.45 μm filter membrane to further remove small impurities, and a clear extract is obtained; 3. Low-temperature concentration: the clear extract is transferred to a rotary evaporator and concentrated under the conditions of a temperature ≤ 40℃ and a vacuum degree of -0.09 MPa until a viscous material with a relative density of 1.2-1.3 is formed, so as to avoid decomposition of the active ingredients caused by high temperature; 4. Freeze-drying: the viscous material is transferred to a tray and pre-frozen for 4 hours in an environment of -40℃ to completely freeze the viscous material; then the pre-frozen material is placed in a vacuum freeze-drying machine and freeze-dried for 24 hours under the conditions of a cold trap temperature of -50℃ and a vacuum degree of 10 Pa to remove water, so as to obtain a dried traditional Chinese medicine extract powder for standby use.

[0014] In some embodiments, the preparation of the active ingredient mixture includes: respectively weighing the Ophiopogon japonicus extract, the Glycyrrhiza uralensis extract, the Pericarpium Citri Reticulatae extract, the Poria cocos extract, the Platycodon grandiflorum extract, the Houttuynia cordata extract, the Lonicera japonica extract, the Siraitia grosvenorii extract, the Mentha haplocalyx extract, and the Emblica officinalis extract powder according to the above mass ratio, and placing all the powders in a mixer to stir for 10-20 minutes, preferably 15 minutes, so as to ensure uniform mixing of the extracts and obtain the active ingredient mixture; wherein all the extract powders need to be pre-screened through a 120-mesh sieve to ensure uniform powder particle size and avoid local concentration unevenness after mixing.

[0015] In some embodiments, the preparation of the chewing gum base includes: placing the edible gum base into an oven, setting the oven temperature to 90℃, and heating for 4 hours to sufficiently soften the gum base; then taking out the softened gum base, stirring uniformly, adding the proportionally weighed flavoring agent, and continuing to stir until the flavoring agent is completely mixed with the gum base; maintaining the temperature of the mixture at 70℃ for standby use to obtain the chewing gum base; the standby temperature of 70℃ can ensure that the gum base maintains a softened state, which is convenient for subsequent mixing with the active ingredient, and at the same time avoids high-temperature damage to the active ingredient.

[0016] In some embodiments, the shaping and aging step includes: Mixing and extruding: the active ingredient mixture is added to the standby chewing gum base, and quickly stirred until the two are completely mixed and uniform; then the mixture is cooled to 25℃ to preliminarily solidify, transferred to a mold, and extruded into a strip-shaped candy embryo by an extrusion device; Cutting and aging: the strip-shaped candy embryo is cut into single-piece thin slices with a weight of 2.5 g; the cut thin slices are placed in a 4℃ environment to cool and age for 2 hours to stabilize the structure of the candy embryo and make the taste more delicate, and finally the traditional Chinese medicine extract chewing gum for assisting smoking cessation is obtained.

[0017] The present application has the following beneficial effects relative to the prior art: The present application builds a double physiological conditioning path of "clearing smoke toxin and moistening lung and spleen" through the "monarch, minister, assistant and guide" combination of 10 kinds of medicinal and edible Chinese medicines: the monarch medicine Houttuynia cordata and honeysuckle can efficiently clear the smoke toxin in the lungs, reducing the damage of nicotine metabolites to organs; the minister medicine Ophiopogon japonicus, Momordica grosvenorii and Emblica officinalis can nourish lung yin, relieving dry cough and throat itching caused by smoking; the assistant medicine Platycodon grandiflorum, Citrus reticulata and Poria cocos can promote lung and spleen and remove dampness, improving the symptoms of difficult expectoration and spleen deficiency; and the guide medicine Glycyrrhiza uralensis and Mentha can adjust the drug properties and quickly relieve sore throat. Experimental data show that the remission rate of somatic withdrawal symptoms of the smoking cessation population using the product of the present application is high, and there is no any side effect; in the nicotine dependence experiment of mice, the "nicotine box" residence time of the high active ingredient group is close to the normal control group after 21 days of administration, which is significantly better than the model control group and the low active ingredient group, proving that the product of the present application can effectively reduce nicotine dependence and assist in achieving physiological smoking cessation.

[0018] The present application adopts a chewing gum dosage form, the chewing action of which can accurately simulate the oral action (such as holding a cigarette and biting) during smoking, filling the "oral window" during smoking cessation and transferring the psychological dependence of smokers on smoking; at the same time, the chewing process of chewing gum can last for more than 30 minutes, which matches the duration of smoking behavior and can long-term distract the attention of smokers. Compared with the existing tablet dosage form and nicotine patch, the present application improves the remission rate of psychological dependence, and clinical follow-up shows that the relapse rate of the smoking cessation population using the product is less than 18% in 3 months, which is much lower than the prior art.

[0019] The edible gum base selected by the present application has excellent drug release performance, which can slowly release the active ingredients to the oral mucosa, and then be absorbed into the blood circulation through the mucosa, avoiding the defect of "fast release and fast failure" of oral tablets; experimental verification shows that the present application has a long effective action time of drugs, which can continuously relieve the craving for cigarettes, and is especially suitable for people with frequent attacks of the craving for cigarettes. In addition, the slow release of the gum base can also avoid the one-time large intake of active ingredients, reduce the metabolic burden of the body, and improve the safety of use.

[0020] The present application adopts the extraction process of "low-temperature immersion extraction and vacuum freeze drying", which can improve the retention rate of heat-sensitive active ingredients such as peppermint volatile oil and honeysuckle chlorogenic acid compared with the existing conventional high-temperature decoction process; wherein, the rotary concentration temperature ≤40℃ and the freeze drying temperature -50℃ can maximize the avoidance of decomposition of active ingredients due to high temperature, ensuring the stability of the efficacy of each extract. At the same time, the pretreatment of 120 mesh screen and 15 minutes of uniform mixing can ensure the uniform distribution of active ingredients in the chewing gum, avoiding the problems of excessive or insufficient local drug efficacy, and further improving the stability of the curative effect of the product.

[0021] The present application can effectively mask the slight bitterness of the traditional Chinese medicine extract by adding natural fragrances, imparting a fresh taste to the chewing gum; at the same time, the momordica grosvenori extract itself has a natural sweetness, which can assist in improving the taste and avoiding the health risks brought by the addition of artificial sweeteners. Clinical research shows that more than 85% of smokers think that the taste of the product of the present application is better than that of the existing nicotine chewing gum, and it is convenient to chew, which can be used in various scenes such as public places, work breaks, etc., without special operation, and the use compliance is significantly improved.

[0022] The 10 kinds of traditional Chinese medicine extracts of the present application are all medicine-food homologous categories, meet the food safety standards, have no side effects of chemical drugs, and are suitable for smokers of different ages; at the same time, the product does not contain nicotine, avoiding the risk of secondary dependence, especially suitable for people who are not tolerant to nicotine replacement therapy, and the application range is much wider than that of the existing chemical smoking cessation method. DETAILED DESCRIPTION

[0023] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0024] General performance verification 1. Experimental animal preparation: 76 SPF C57BL / 6 male mice weighing 17-22 g were selected, and adaptive feeding was carried out for 7 days, the feeding environment temperature was 22±2℃, the humidity was 50±5%, the light and dark cycle was 12h, and the mice were free to eat and drink water.

[0025] 2. Nicotine dependence model construction: 6 mice were randomly selected as a blank control group (conventional feeding, no nicotine treatment), and the remaining 70 mice were used as a model group. The model group was subcutaneously injected with 0.5mg / kg nicotine solution every day for 21 days; from the 15th day of self-administration, the model group mice were trained in the conditioned place preference device (containing a black "nicotine box" and a white neutral box): 1h in the "nicotine box" after administration, and free exploration during non-administration; the blank control group always freely explored. After 7 days of training, the mice were withdrawn for 24h, and the residence time of the mice in the "nicotine box" within 900s (recorded as D0) was tested. When the residence time of the model group was significantly longer than that of the blank control group, the modeling was considered successful.

[0026] 3. Grouping and administration: 50 mice with successful modeling were evenly divided into model control group, example 1-3 group, comparative example 1-2, 4-7 group according to body weight and D0 residence time, 5 mice in each group. The mice in each experimental group were orally administered with simulated chewing drug solution of corresponding chewing gum (preparation method: corresponding chewing gum was added into 50 mL of normal saline, and the supernatant was taken after the chewing for 10 min at 37℃ using a CS-4.8 type oral chewing abrasion simulation tester), with a frequency of 3 times a day and a dose of 1 mL / kg, for 21 consecutive days; the model control group was orally administered with simulated chewing drug solution of comparative example 3 (blank chewing gum), and the blank control group was not administered with drugs. The blank chewing gum solution used in the model control group was comparative example 3 sample, and no other animal group was set.

[0027] 4. Performance test: the conditioned place preference test was performed on the mice in each group on the 7th day (D7), the 14th day (D14), and the 21st day (D21) of administration, with a time of 900 s, and the residence time of the mice in the "nicotine box" was recorded.

[0028] 5. Data statistics: the data was analyzed using R4.5.0 software, the measurement data was represented as "mean ± standard deviation (x ± s, n = 5)", and the normality and variance homogeneity were verified by Leven's test. If the normality and variance homogeneity were met (P > 0.05), the single factor analysis of variance (ANOVA) combined with LSD test was used, and the non-normal homogeneity data was subjected to Kruskal-Wallis test combined with Dunnett's test. Statistical significance was marked as: **P < 0.01 compared with the blank control group, #P < 0.05 compared with the model control group, and ##P < 0.01 compared with the model control group.

[0029] The raw materials of each example and comparative example are as follows

[0030] Example 1 Preparation steps Step 1: Preparation of traditional Chinese medicine extract. Ophiopogon japonicus, licorice, dried tangerine or orange peel, poria cocos, platycodon grandiflorum, houttuynia cordata, honeysuckle, momordica grosvenori, peppermint, and emblica were taken as raw materials, each raw material was mixed with purified water at a ratio of 1:10 (w / v), sealed, and then immersed and extracted at 25℃ for 72 h in the dark, with stirring every 12 h during the extraction. After the extraction was completed, the extract was centrifuged at 8000 rpm for 15 min, and the supernatant was filtered through a 0.45 μm filter membrane. The filtered clear extract was transferred to a rotary evaporator and concentrated to a viscous substance with a relative density of 1.25 under the conditions of a temperature ≤40℃ and a vacuum degree of-0.09 MPa. The viscous substance was transferred to a tray, pre-frozen at-40℃ for 4 h, and then placed in a vacuum freeze-drying machine for freeze-drying under the conditions of a cold trap temperature of-50℃ and a vacuum degree of 10 Pa for 24 h to obtain a traditional Chinese medicine extract powder, which was ready for use.

[0031] Step 2: Preparation of active ingredient mixture. Weigh each traditional Chinese medicine extract according to the mass ratio: Ophiopogon japonicus extract 18%, Glycyrrhiza uralensis extract 2.4%, Citrus reticulata extract 7.5%, Poria cocos extract 7.5%, Platycodon grandiflorum extract 4.98%, Houttuynia cordata extract 7.5%, Lonicera japonica extract 4.98%, Siraitia grosvenorii extract 4.98%, Mentha haplocalyx extract 4.98%, and Phyllanthus emblica extract 4.98%. The powders of the above extracts are sieved through a 120-mesh sieve and stirred in a mixer for 15 min to obtain the active ingredient mixture.

[0032] Step 3: Preparation of chewing gum base. Weigh 31.6% of sugar gum (edible gum base) and place it in an oven. Set the temperature to 90°C and heat for 4 h. Stir every 30 min until the gum base is completely softened. Remove the softened sugar gum and add 0.6% of peppermint essence (flavoring agent). Stir until the essence and gum base are completely mixed. Keep the temperature at 70°C for standby. The chewing gum base is obtained.

[0033] Step 4: Molding and aging. Add the active ingredient mixture to the standby chewing gum base and stir quickly until they are completely mixed and uniform. Then naturally cool to 25°C. Transfer the cooled mixture to a mold and extrude it into a strip-shaped candy embryo using an extrusion device. Cut the strip-shaped candy embryo into thin slices with a single piece weighing 2.5g. Place the slices in a 4°C refrigerator for 2h of cooling and aging. The traditional Chinese medicine extract chewing gum for assisting smoking cessation is obtained.

[0034] Example 2 Preparation steps Step 1: Preparation of traditional Chinese medicine extract. The process is identical to Step 1 of Example 1, and the same powders of 10 traditional Chinese medicine extracts are obtained.

[0035] Step 2: Preparation of active ingredient mixture. Weigh each traditional Chinese medicine extract according to the mass ratio: Ophiopogon japonicus extract 4.5%, Glycyrrhiza uralensis extract 0.6%, Citrus reticulata extract 1.875%, Poria cocos extract 1.875%, Platycodon grandiflorum extract 1.245%, Houttuynia cordata extract 1.875%, Lonicera japonica extract 1.245%, Siraitia grosvenorii extract 1.245%, Mentha haplocalyx extract 1.245%, and Phyllanthus emblica extract 1.245%. The subsequent sieving and stirring steps are consistent with Step 2 of Example 1, and the active ingredient mixture is obtained.

[0036] Step 3: Preparation of chewing gum base. Weigh 82.45% of sugar gum. The subsequent heating, addition of peppermint essence (0.6% by mass), and temperature maintenance steps are consistent with Step 3 of Example 1, and the chewing gum base is obtained.

[0037] Step 4: Molding and aging. The process is identical to Step 4 of Example 1, and the traditional Chinese medicine extract chewing gum for assisting smoking cessation is obtained.

[0038] Example 3 Preparation step Step 1: Preparation of Chinese medicine extract. Take the same 10 kinds of Chinese medicine raw materials as in Example 1, each mixed with purified water at a ratio of 1:10 (w / v), placed in a decoction pot and heated at 100°C for 2h, stirring every 20min during the process; after the decoction is completed, the liquid is centrifuged at 8000rpm for 15min, and the supernatant is filtered through a 0.45μm filter membrane; the clear filtrate is transferred to a rotary evaporator and concentrated to a viscous substance with a relative density of 1.2-1.3 under the conditions of 80°C and normal pressure; the viscous substance is placed in a 60°C air-drying oven for 24h to obtain a Chinese medicine extract powder, which is ready for use.

[0039] Step 2: Preparation of active ingredient mixture. The same as Step 2 of Example 1 (weighing, sieving and stirring according to the proportion of Chinese medicine extract in Example 1), to obtain an active ingredient mixture.

[0040] Step 3: Preparation of chewing gum base. The same as Step 3 of Example 1, to obtain a chewing gum base.

[0041] Step 4: Shaping and aging. The same as Step 4 of Example 1, to obtain a Chinese medicine extract chewing gum for assisting in smoking cessation.

[0042] Comparative Example 1 Preparation step Step 1: Preparation of Chinese medicine extract. The same as Step 1 of Example 1, to obtain 10 kinds of Chinese medicine extract powders.

[0043] Step 2: Preparation of active ingredient mixture. Weigh the Chinese medicine extracts according to the proportion by mass: Ophiopogon japonicus extract 9%, Glycyrrhiza uralensis Fisch extract 1.2%, Citrus reticulata Blanco extract 3.75%, Poria cocos (Schw.) Wolf extract 3.75%, Platycodon grandiflorum Jacq. extract 2.49%, Houttuynia cordata Thunb. extract 3.75%, Lonicera japonica Thunb. extract 2.49%, Siraitia grosvenorii Swingle extract 2.49%, Mentha haplocalyx Briq. extract 2.49%, and Emblica officinalis Gaertn. extract 2.49%; the subsequent sieving and stirring steps are the same as Step 2 of Example 1, to obtain an active ingredient mixture.

[0044] Step 3: Preparation of chewing gum base. Weigh sugar gum at a proportion of 65.5% by mass, and add peppermint essence at a proportion of 0.6% by mass; the subsequent heating and holding steps are the same as Step 3 of Example 1, to obtain a chewing gum base.

[0045] Step 4: Shaping and aging. The same as Step 4 of Example 1, to obtain a chewing gum.

[0046] Comparative Example 2 Preparation step Step 1: Preparation of Chinese medicine extract. The same as Step 1 of Example 1, 10 kinds of Chinese medicine extract powders were obtained.

[0047] Step 2: Preparation of active ingredient mixture. The Chinese medicine extracts were weighed according to the mass ratio: Ophiopogon japonicus extract 6%, Glycyrrhiza uralensis Fisch extract 0.8%, Citrus reticulata Blanco extract 2.5%, Poria cocos (Schw.) Wolf extract 2.5%, Platycodon grandiflorum Jacq extract 1.66%, Houttuynia cordata Thunb extract 2.5%, Lonicera japonica Thunb extract 1.66%, Siraitia grosvenorii Swingle extract 1.66%, Mentha haplocalyx Briq extract 1.66%, and Emblica officinalis Gaertn extract 1.66%; the subsequent sieving and stirring steps were the same as Step 2 of Example 1, and an active ingredient mixture was obtained.

[0048] Step 3: Preparation of chewing gum base. Sugar gum tree gum with a mass ratio of 76.8% was weighed, and 0.6% of peppermint essence was added; the subsequent heating and incubation steps were the same as Step 3 of Example 1, and a chewing gum base was obtained.

[0049] Step 4: Shaping and aging. The same as Step 4 of Example 1, and chewing gum was obtained.

[0050] Comparative Example 3 Preparation steps Step 1: Preparation of chewing gum base. Sugar gum tree gum with a mass ratio of 99.4% was weighed, and the mixture was heated in an oven at 90°C for 4 h until completely softened, and 0.6% of peppermint essence was added; after stirring uniformly, the mixture was kept at 70°C for standby, and a chewing gum base was obtained.

[0051] Step 2: Shaping and aging. The chewing gum base was naturally cooled to 25°C, transferred to a mold, extruded into a strip-shaped sugar embryo, cut into 2.5 g / slice thin slices, and cooled and aged at 4°C for 2 h, and a blank chewing gum (without any Chinese medicine extract) was obtained.

[0052] Comparative Example 4 Preparation steps Step 1: Preparation of Mentha haplocalyx Briq extract. The Mentha haplocalyx Briq extract powder was prepared according to Step 1 of Example 1, and was standby.

[0053] Step 2: Preparation of active ingredient mixture. The Mentha haplocalyx Briq extract powder with a mass ratio of 49.98% (consistent with the total ratio of 10 kinds of Chinese medicine extracts in Example 1) was sieved through a 120-mesh sieve and stirred for 15 min, and an active ingredient mixture was obtained.

[0054] Step 3: Preparation of chewing gum base. Sugar gum tree gum with a mass ratio of 49.42% was weighed, and 0.6% of peppermint essence was added; the subsequent heating and incubation steps were the same as Step 3 of Example 1, and a chewing gum base was obtained.

[0055] Step 4: Shaping and aging. The same as Step 4 of Example 1, and chewing gum was obtained.

[0056] Comparative Example 5 Preparation Steps Step 1: Preparation of Traditional Chinese Medicine Extracts. Ophiopogon japonicus extract, Glycyrrhiza uralensis extract, Citrus reticulata extract, Poria cocos extract, Platycodon grandiflorum extract, Siraitia grosvenorii extract, Mentha haplocalyx extract, Phyllanthus emblica extract were prepared according to Step 1 of Example 1. Meanwhile, Crataegus pinnatifida extract and Hordeum vulgare extract were prepared according to the same process to replace original monarch herbs of Houttuynia cordata and Lonicera japonica, respectively, for standby use.

[0057] Step 2: Preparation of Active Ingredient Mixture. Ophiopogon japonicus extract 18%, Glycyrrhiza uralensis extract 2.4%, Citrus reticulata extract 7.5%, Poria cocos extract 7.5%, Platycodon grandiflorum extract 4.98%, Crataegus pinnatifida extract 7.5% (replacing Houttuynia cordata), Hordeum vulgare extract 4.98% (replacing Lonicera japonica), Siraitia grosvenorii extract 4.98%, Mentha haplocalyx extract 4.98%, and Phyllanthus emblica extract 4.98% were weighed according to the mass ratio. The subsequent sieving and stirring steps were consistent with Step 2 of Example 1 to obtain the active ingredient mixture.

[0058] Step 3: Preparation of Chewing Gum Base. The process was completely consistent with Step 3 of Example 1 (chicle 31.6%, peppermint essence 0.6%) to obtain the chewing gum base.

[0059] Step 4: Shaping and Aging. The process was completely consistent with Step 4 of Example 1 to obtain the chewing gum.

[0060] Comparative Example 6 Preparation Steps Step 1: Preparation of Active Ingredient Mixture. Coffee beans, Agastache rugosa, and Rubus suavissimus raw materials were ground into powders and passed through a 120-mesh sieve. Coffee extract 20%, Agastache rugosa extract 15%, and Rubus suavissimus extract 14.98% (total mass ratio 49.98%, consistent with the total mass ratio of traditional Chinese medicines in Example 1) were weighed according to the mass ratio, and then placed in a mixer for stirring for 15 min to obtain the active ingredient mixture.

[0061] Step 2: Preparation of Chewing Gum Base. Chicle with a mass ratio of 49.42% was weighed, and peppermint essence with a mass ratio of 0.6% was added. The subsequent heating and holding steps were consistent with Step 3 of Example 1 to obtain the chewing gum base.

[0062] Step 3: Shaping and Aging. The process was completely consistent with Step 4 of Example 1 to obtain the chewing gum.

[0063] Comparative Example 7 Preparation Steps Step 1: Preparation of Traditional Chinese Medicine Extracts. The process was completely consistent with Step 1 of Example 1 to obtain powders of 10 traditional Chinese medicine extracts.

[0064] Step 2: Preparation of Active Ingredient Mixture. The process was completely consistent with Step 2 of Example 1 to obtain the active ingredient mixture.

[0065] Step 3: Preparation of chewing gum base. Weigh 31.6% carrageenan (replace sugar gum base), add appropriate amount of pure water, stir at room temperature until the carrageenan is completely dissolved; add 0.6% peppermint flavor, stir evenly and keep at room temperature, get chewing gum base (carrageenan does not need high temperature heating).

[0066] Step 4: molding and aging. Add the active ingredient mixture to the carrageenan base, stir evenly, then transfer to the mold, cool to 25℃ at room temperature to form a strip-shaped embryo, cut into 2.5g / slice of thin slices, 4℃ cooling aging 2h, get chewing gum (the chewing gum is completely dissolved within 10min).

[0067] The performance verification results of the above examples and comparative examples are as follows:

[0068] All chewing gums containing 10 traditional Chinese medicine extracts have a monotonic decrease in "nicotine box residence time" as the number of days of administration increases; the decline slope is positively correlated with the total amount of active ingredients. The high-dose group (Example 1, 49.98% extract) was close to the blank control level (482.5s vs 445.8s, P>0.05) on the 21st day, indicating that nicotine dependence was basically eliminated; the low-dose group (Example 2, 16.95% extract) only decreased to 652.7s, which was still 46% higher than the blank group, with limited efficacy.

[0069] Formulation integrity comparison Example 1 (10 full prescriptions) D21 residence time 482.5s; Comparative example 4 (only retain peppermint) 669.8s, comparative example 5 (replace the monarch drug with hawthorn / malt) 648.9s; There was no statistical difference between the two control groups throughout the process (P>0.05), which proved that "clearing smoke toxin and moistening lung and spleen" full prescription is indispensable.

[0070] Preparation process comparison Example 1 (low temperature immersion + freeze drying) D21 residence time 482.5s; Example 3 (100℃ decoction + hot air drying) D21 residence time 568.7s; Low-temperature process improves efficacy by 18% and shows a very significant difference 7 days earlier (D7 residence time 623.4s vs 678.3s).

[0071] Gum base type comparison Example 1 (sugar gum base) D21 residence time 482.5s; Comparative example 7 (carrageenan) D21 residence time 627.3s; And carrageenan chewing gum group completely dissolved within 10 min, unable to maintain more than 30 min sustained-release and oral replacement action, efficacy decreased by 30%.

[0072] Dose-effect relationship is clear: the total amount of active ingredients ≥25% can produce a very significant effect of smoking cessation (##P<0.01).

[0073] Compatibility is irreplaceable: lack of monarch drug (Houttuynia cordata / honeysuckle) or single mint can not reduce nicotine preference (P>0.05).

[0074] Process determines activity: low temperature extraction makes the retention rate of heat-sensitive components (chlorogenic acid, menthol) increase by more than 20%, which is directly converted into behavioral advantage.

[0075] Gum base determines behavior replacement: the "chewing-resistant-sustained-release" dual function of sugar gum base is the necessary condition for psychological replacement, and non-chewing-resistant gum base (carrageenan) is ineffective even if it contains the same medicine.

[0076] Traditional Chinese medicine extract is the only source of efficacy: blank gum base (comparative example 3) has no difference with the model group, excluding the interference of the auxiliary material itself.

[0077] In summary, example 1 meets the four elements of "high dose-full recipe-low temperature process-chewing-resistant gum base", so it realizes the dual goals of physiological smoking cessation and psychological replacement within 21 days, and the relapse rate is less than 18% in 3 months, which is significantly better than the prior art.

[0078] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A chewing gum made from traditional Chinese medicine extracts for assisting smoking cessation, characterized in that, The raw materials of the herbal extract chewing gum, calculated by weight percentage (100%), include: 4.5-18% Ophiopogon japonicus extract, 0.6-2.4% Glycyrrhiza uralensis extract, 1.875-7.5% Citrus reticulata peel extract, 1.875-7.5% Poria cocos extract, 1.245-4.98% Platycodon grandiflorus extract, 1.875-7.5% Houttuynia cordata extract, 1.245-4.98% Lonicera japonica extract, 1.245-4.98% Siraitia grosvenorii extract, 1.245-4.98% Mentha haplocalyx extract, 1.245-4.98% Phyllanthus emblica extract, 31.6-82.45% edible gum base, and 0.4-0.8% flavoring agent.

2. The chewing gum made from traditional Chinese medicine extracts for assisting smoking cessation as described in claim 1, characterized in that, The extracts of Ophiopogon japonicus, Glycyrrhiza uralensis, Citrus reticulata, Poria cocos, Platycodon grandiflorus, Houttuynia cordata, Lonicera japonica, Siraitia grosvenorii, Mentha haplocalyx, and Phyllanthus emblica were all prepared through the following steps: Mix a single Chinese herbal raw material with purified water at a ratio of 1:10 (w / v), seal the mixture, and extract it by soaking in the dark at 20-30℃ for 72 hours, stirring once every 12 hours during the process. The extract was centrifuged at 8000 rpm for 15 min and filtered through a 0.45 μm filter membrane. Then, it was concentrated to a viscous substance with a relative density of 1.2-1.3 under conditions of temperature ≤40℃ and vacuum degree -0.09 MPa. The viscous substance was pre-frozen at -40℃ for 4 hours, and then vacuum freeze-dried at -50℃ and 10Pa for 24 hours to obtain a single Chinese herbal extract.

3. The chewing gum made from traditional Chinese medicine extracts for assisting smoking cessation as described in claim 1, characterized in that, The edible gum base is selected from one or more of natural gums, synthetic rubber, and resins; wherein, the natural gums include at least one of gum arabic, gum palm, and gum balata; the synthetic rubbers include at least one of styrene-butadiene rubber, butyl rubber, and polyisobutylene; and the resins include at least one of rosin glycerol ester, wood rosin glycerol ester, and polymerized rosin glycerol.

4. The chewing gum made from traditional Chinese medicine extracts for assisting smoking cessation as described in claim 1, characterized in that, The fragrance is selected from one or more of the following: strawberry flavoring, cherry flavoring, peppermint flavoring, menthol, vanilla flavoring, and orange flavoring.

5. The chewing gum made from traditional Chinese medicine extracts for assisting smoking cessation as described in claim 1, characterized in that, The herbal extract chewing gum is in the form of a sheet, with each sheet weighing 2.5g. The herbal extract chewing gum is prepared by cooling and aging at 4°C for 2 hours.

6. A method for preparing a chewing gum made from traditional Chinese medicine extracts for assisting smoking cessation as described in any one of claims 1-5, characterized in that, Includes the following steps: (1) Prepare extracts of Ophiopogon japonicus, Glycyrrhiza uralensis, Citrus reticulata, Poria cocos, Platycodon grandiflorus, Houttuynia cordata, Lonicera japonica, Siraitia grosvenorii, Mentha haplocalyx, and Phyllanthus emblica; (2) Weigh each extract and excipient according to the mass ratio described in claim 1, mix all extracts to obtain an extract mixture; (3) Heat the edible gum base and then mix it with the flavoring agent to obtain the chewing gum base; (4) Mix the extract mixture with the chewing gum base and cool it. Then, put it into a mold and press it to obtain the sugar embryo. (5) Cut the sugar embryo, cool and age the cut sugar embryo to obtain the Chinese herbal extract chewing gum used to assist in smoking cessation.

7. The preparation method according to claim 6, characterized in that, The extracts of Ophiopogon japonicus, Glycyrrhiza uralensis, Citrus reticulata, Poria cocos, Platycodon grandiflorus, Houttuynia cordata, Lonicera japonica, Siraitia grosvenorii, Mentha haplocalyx, and Phyllanthus emblica mentioned in step (1) are all prepared through the following steps: Mix a single Chinese herbal raw material with purified water at a ratio of 1:10 (w / v), seal the mixture, and extract it by soaking in the dark at 20-30℃ for 72 hours, stirring once every 12 hours during the process. The extract was centrifuged at 8000 rpm for 15 min and filtered through a 0.45 μm filter membrane. Then, it was concentrated to a viscous substance with a relative density of 1.2-1.3 under conditions of temperature ≤40℃ and vacuum degree -0.09 MPa. The viscous substance was pre-frozen at -40℃ for 4 hours, and then vacuum freeze-dried at -50℃ and 10Pa for 24 hours to obtain a single Chinese herbal extract.

8. The preparation method according to claim 6, characterized in that, In step (3), the specific conditions for heat treatment of the edible gum base are as follows: heat to 90°C in an oven and maintain the temperature at 90°C for 4 hours, stirring evenly during the heating process; after the edible gum base is mixed with the flavoring agent, keep the temperature of the chewing gum base at 70°C for later use.

9. The preparation method according to claim 6, characterized in that, In step (4), the active ingredient mixture is mixed with the chewing gum base, cooled to 25°C, and then put into the mold for extrusion.

10. The preparation method according to claim 6, characterized in that, In step (5), the specific operation of cutting the sugar embryo is to cut the sugar embryo into thin slices with a weight of 2.5g / slice; the specific conditions for cooling and aging are: to place it at 4℃ for 2 hours.

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