Use of a traditional Chinese medicine composition in treating tinnitus

Abstract

The present invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition and its use. The present invention is a new use of the traditional Chinese medicine composition developed on the basis of patent ZL200410073958.X, and the traditional Chinese medicine composition is mainly prepared from immature bitter orange, white atractylodes, ginseng, wolfberry, donkey-hide gelatin, polygonum multiflorum, cassia seed and aloe. Pharmacological experiments have shown that the traditional Chinese medicine composition of the present invention can effectively prevent or treat tinnitus.

Description

Technical Field

[0001] The invention relates to a new use of a traditional Chinese medicine composition, and in particular to use of the traditional Chinese medicine composition in preparing a medicine for preventing, treating or improving tinnitus, and belongs to the technical field of traditional Chinese medicine. Background Art

[0002] Tinnitus is the result of different pathological changes of many diseases involving the auditory system. The etiology is complex and the mechanism is unclear. It is mainly manifested as the subjective perception of sound in the ear or brain without corresponding external sound source or electrical stimulation. Clinically, it is both a concomitant symptom of many diseases and the first symptom of some serious diseases (such as acoustic neuroma).

[0003] Senile tinnitus is a natural physiological process. As people age, their organs begin to decline, and hearing becomes increasingly worse. A group of American data reported that the prevalence rate for people aged 55 to 64 is 9%, and for people aged 65 to 74 is 11%, with more women than men. Many people with tinnitus have normal hearing, while some elderly people often have severe deafness. Elderly people are prone to tinnitus. In mild cases, it seems as if there is a distant cicada chirping in the ears, and in severe cases, it is like a whistle or even a drum. The buzzing sound day and night makes the elderly uneasy, affects their sleep and life, and is bound to affect their physical health. It is indeed a distressing disease. If the tinnitus is caused by tension, fatigue, or neurasthenia, it is mostly caused by mental workers who continuously overuse their brains. After proper rest, the tinnitus can improve and disappear. Tinnitus caused by ischemia and hypoxia of the auditory center, auditory nerve and auditory organ endings due to high or low blood pressure, anemia, arteriosclerosis or insufficient blood supply, etc. should be focused on treating the main disease. Tinnitus can gradually improve.

[0004] Chinese patent ZL200410073958.X discloses a composition with laxative, detoxifying, weight loss and lipid-lowering functions and its preparation method. The composition is composed of eight Chinese medicinal herbs, including Polygonum multiflorum, aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala, and Citrus aurantium, and has a good therapeutic effect on constipation caused by internal toxicity and yin fluid deficiency. The relevant product has been launched on the market, and the product name is "Shouhui Tongbian Capsule". Summary of the invention

[0005] The use of the present invention is derived from clinical feedback that some elderly patients found that their tinnitus was alleviated during the period of taking Shouhui Tongbian Capsules to treat functional constipation.

[0006] Based on the clinical feedback of Shouhui Tongbian Capsule, the inventor conducted further research on the new use of Shouhui Tongbian Capsule and its formula in treating or improving tinnitus. The research results confirmed that Shouhui Tongbian Capsule and its formula have good effects in preventing, treating or improving tinnitus.

[0007] One of the purposes of the present invention is to provide a use of a Chinese medicine composition mainly composed of Polygonum multiflorum, Cassia seed, aloe, Lycium barbarum, donkey-hide gelatin and ginseng in preparing a medicine for treating or improving tinnitus.

[0008] Specifically, the above-mentioned Chinese medicine composition is mainly composed of the following raw materials:

[0009] 25-400 parts by weight of Polygonum multiflorum 30-500 parts by weight of Cassia seed 30-600 parts by weight of Aloe vera

[0010] 30-150 parts by weight of wolfberry 30-150 parts by weight of donkey hide gelatin 20-100 parts by weight of ginseng

[0011] Fructus Aurantii Immaturus 50-200 parts by weight, Atractylodes macrocephala 20-100 parts by weight.

[0012] Preferably, the above-mentioned Chinese medicine composition is mainly composed of the following raw materials:

[0013] 60-150 parts by weight of Polygonum multiflorum 80-180 parts by weight of Cassia seed 100-200 parts by weight of Aloe vera

[0014] 30-100 parts by weight of wolfberry 30-100 parts by weight of donkey hide gelatin 20-80 parts by weight of ginseng

[0015] Fructus Aurantii Immaturus 80-150 parts by weight, Atractylodes macrocephala 20-80 parts by weight.

[0016] Further preferably, the above-mentioned Chinese medicine composition is mainly composed of the following raw materials:

[0017] 80-120 parts by weight of Polygonum multiflorum 100-150 parts by weight of Cassia seed 120-160 parts by weight of Aloe vera

[0018] 50-80 parts by weight of wolfberry 40-80 parts by weight of donkey hide gelatin 20-50 parts by weight of ginseng

[0019] 80-120 parts by weight of Citrus aurantium and 30-50 parts by weight of Atractylodes macrocephala.

[0020] The tinnitus described in the present invention mainly refers to senile tinnitus.

[0021] Preferably, the senile tinnitus may be caused by cardiovascular system diseases, ototoxic drugs or psychological factors.

[0022] The tinnitus described in the present invention can be of wind-heat disturbance type, liver fire blazing type, phlegm turbidity type, phlegm blocking the clear orifices type, kidney essence deficiency type or spleen qi failure type according to TCM syndrome differentiation.

[0023] The second object of the present invention is to provide a preparation prepared from the above-mentioned Chinese medicine composition, which can be prepared into a clinically acceptable dosage form alone or after adding pharmaceutically acceptable excipients.

[0024] Preferably, the clinically acceptable dosage form may be capsules, tablets, granules, pills, powders, or oral liquid preparations such as oral liquids and syrups.

[0025] The third object of the present invention is to provide the use of Shouhui Tongbian Capsules prepared from the above-mentioned Chinese medicine composition in the preparation of drugs for preventing, treating or improving tinnitus.

[0026] Preferably, the tinnitus refers to senile tinnitus.

[0027] The fourth object of the present invention is to provide a method for preparing the above-mentioned Shouhui Tongbian Capsule, and the preparation steps are as follows:

[0028] (1) Grind donkey-hide gelatin into fine powder, pass through an 80-mesh sieve, and set aside;

[0029] (2) Ginseng, Polygonum multiflorum, Cassia seed, and aloe were extracted with 60% ethanol for 2 times of reflux, with 10 times of ethanol added for the first time and 8 times of ethanol added for the second time. Each extraction lasted for 2 hours. The filtrates were combined and filtrate I was obtained for later use.

[0030] (3) Add water to wolfberry, Atractylodes macrocephala, and Citrus aurantium and decoct twice. For the first decoction, add 8 times the amount of water, soak for 1 hour, decoct for 1.5 hours, and filter. For the second decoction, add 6 times the amount of water, decoct for 1.5 hours, and filter. Combine the filtrates and concentrate to a clear paste with a relative density of 1.10 to 1.20 (80°C). Place at room temperature, stir, add ethanol to make the purity reach 60% (20°C), refrigerate and let stand for more than 24 hours, filter, and obtain filtrate II for later use.

[0031] (4) combining the filtrate I obtained in step (2) with the filtrate II obtained in step (3), concentrating the mixture to a thick paste having a relative density of 1.30-1.35 (70° C.), drying and crushing the mixture, adding the fine donkey-hide gelatin powder prepared in step (1) and an appropriate amount of dextrin, mixing the mixture evenly, dry granulating the mixture, and encapsulating the mixture to obtain the product.

[0032] Compared with the prior art, the present invention has achieved remarkable technical effects:

[0033] (1) The Chinese medicine composition of the present invention can effectively prevent tinnitus caused by sodium salicylate and reduce the amplitude of AS reaction in mice.

[0034] (2) The Chinese medicine composition of the present invention can effectively treat tinnitus caused by sodium salicylate and significantly prolong the extinction period of the conditioned reflex of "sound appears - drinking starts, sound disappears - drinking stops" in rats. DETAILED DESCRIPTION

[0035] The following examples are provided to further disclose the present invention. It should be noted that these examples are only preferred embodiments of the present invention and do not limit the scope of protection claimed in the present invention.

[0036] Example 1 Commercially available Shouhui laxative capsules

[0037]

Ingredients

[0038] [Functions and indications] Nourishes yin and replenishes qi, eliminates turbidity and relieves constipation. It is used for functional constipation, and for patients with deficiency of both qi and yin and internal accumulation of toxic evil according to TCM diagnosis, with symptoms of constipation, abdominal distension, dry mouth and throat, fatigue, fever in the five parts of the body, red and tender or pale tongue, white or greasy tongue coating, deep and thin or slippery and rapid pulse.

[0039] Example 2 Capsule Preparation

[0040] Polygonum multiflorum 25g Cassia seed 500g Aloe vera 30g

[0041] 150g wolfberry, 30g donkey hide gelatin, 100g ginseng

[0042] Citrus aurantium 50g, Atractylodes macrocephala 100g;

[0043] Take the prescribed amount of donkey-hide gelatin and crush it into fine powder, pass it through an 80-mesh sieve, and set aside; take the prescribed amount of ginseng, Polygonum multiflorum, Cassia seed, and aloe, add 60% ethanol to reflux and extract twice, add 10 times the amount for the first time, add 8 times the amount for the second time, extract for 2 hours each time, filter them separately, combine the filtrate, and obtain filtrate I; take the prescribed amount of wolfberry, Atractylodes macrocephala, and Citrus aurantium, add water and decoct twice, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, filter, add 6 times the amount of water for the second time, decoct for 1.5 hours When the temperature is reached, filter, combine the filtrates, concentrate to a clear paste with a relative density of 1.10-1.20 (80°C), place at room temperature, stir, add ethanol to make the purity reach 60% (20°C), refrigerate and let stand for more than 24 hours, filter to obtain filtrate II; combine filtrate I and filtrate II, concentrate to a thick paste with a relative density of 1.30-1.35 (70°C), dry, crush, add fine donkey-hide gelatin powder and an appropriate amount of dextrin, mix well, dry granulate, put into capsules, and make 1000 capsules.

[0044] Example 3 Pill Preparation

[0045] Polygonum multiflorum 400g Cassia seed 30g Aloe vera 600g

[0046] 30g wolfberry, 150g donkey hide gelatin, 20g ginseng

[0047] Zhishi 200g, Baizhu 20g;

[0048] Refer to the preparation method described in Example 2.

[0049] Example 4 Preparation of granules

[0050] Polygonum multiflorum 60g Cassia seed 180g Aloe vera 100g

[0051] 100g wolfberry, 30g donkey hide gelatin, 80g ginseng

[0052] Citrus aurantium 80-g, Atractylodes macrocephala 80g.

[0053] Refer to the preparation method described in Example 2.

[0054] Example 5 Capsule Preparation

[0055] Polygonum multiflorum 150g Cassia seed 80g Aloe vera 200g

[0056] 30g wolfberry, 100g donkey hide gelatin, 20g ginseng

[0057] 150g of Citrus aurantium and 20g of Atractylodes macrocephala.

[0058] Refer to the preparation method described in Example 2.

[0059] Example 6 Capsule Preparation

[0060] Polygonum multiflorum 80g Cassia seed 150g Aloe vera 120g

[0061] 80g wolfberry, 40g donkey hide gelatin, 50g ginseng

[0062] Citrus aurantium 80g, Atractylodes macrocephala 50g.

[0063] Refer to the preparation method described in Example 2.

[0064] Example 7 Capsule Preparation

[0065] Polygonum multiflorum 120g Cassia seed 100g Aloe vera 160g

[0066] 50g wolfberry, 80g donkey hide gelatin, 20g ginseng

[0067] 120g of Citrus aurantium and 30g of Atractylodes macrocephala.

[0068] Refer to the preparation method described in Example 2.

[0069] Pharmacodynamics experiments

[0070] In order to verify the efficacy of the Chinese herbal composition of the present invention in treating tinnitus, the inventors conducted the following animal experimental studies. Only some experimental models are used as examples for illustration. The inventors also conducted pharmacological experimental studies on tinnitus caused by other reasons and other Chinese herbal composition formulas recorded in the specification, all of which can achieve the same or similar effects, which will not be described one by one here.

[0071] The inventors would like to explain that the following experimental studies were conducted on the basis of the acute toxicity test and the long-term toxicity test to prove the safety of the drug, and the dosages used in the experimental studies were all within the safe dosage range.

[0072] 1. The preventive effect of the Chinese medicine composition of the present invention on tinnitus.

[0073] 1 Materials

[0074] 1.1 Animals:

[0075] Kunming mice, SPF grade, weighing 18-22 g, experimental animal license number: SYXK(Lu)2018 0008, were provided by Lunan Pharmaceutical Group Co., Ltd. and were adaptively raised for one week before the experiment.

[0076] 1.2 Drugs and reagents

[0077] 1.2.1 Drugs

[0078] Shouhui Tongbian Capsules (National Medicine Standard Z20150041) are available on the market and are produced by Lunan Houpu Pharmaceutical Co., Ltd.

[0079] Example 2 Capsules obtained

[0080] 1.2.3 Dosage for mice

[0081] Shouhui Tongbian Capsule: 0.378g / kg (high dose), 0.189g / kg (medium dose), 0.0945g / kg (low dose);

[0082] Example 2 capsule: 0.189 g / kg;

[0083] 2. Experimental Method

[0084] 2.1 Grouping, modeling and drug administration

[0085] 60 mice were randomly divided into a blank group, a model group, three dose groups of Shouhui Tongbian Capsules (high, medium and low), and Example 2 group, with 10 mice in each group. The model group, the three dose groups of Shouhui Tongbian Capsules, and Example 2 group were given intraperitoneal injection of sodium salicylate (400 mg / kg), and the blank group was injected with an equal amount of normal saline once a day for 3 consecutive days; at the same time, the three dose groups of Shouhui Tongbian Capsules and Example 2 group were given corresponding drugs by gavage, and the blank group and the model group were given an equal amount of normal saline by gavage.

[0086] 2.2 Detection indicators

[0087] Two hours after the last administration, auditory startle (AS) response and gap inhibition auditory startle (GPIAS) response tests were performed.

[0088] The experimental principle is that animals with normal hearing function will startle reflexively when they suddenly hear a loud startling sound, a phenomenon known as the AS reaction. When a silent gap is inserted into the process of the experimental animals receiving continuous low-loudness and narrow-band noise (background noise) stimulation of different frequencies, mice with normal hearing function can perceive the appearance of this silent gap and thus become alert, and the amplitude of the startle reaction to the loud sound that follows will be greatly reduced. However, mice with tinnitus, especially when the frequency of the tinnitus is consistent with the frequency of the background noise, cannot distinguish the existence of the gap due to the existence of their own tinnitus and therefore will not become alert, and will still startle with a large amplitude to the subsequent loud stimulus sound. The ratio of the AS reaction amplitude of mice obtained in the paired experiment using a background noise without a silent gap and a background noise with a silent gap as the background stimulus sound is used to determine whether the mouse has tinnitus.

[0089] GPIAS consists of 100 gap trials and 100 non-gap trials, and the gap trials and non-gap trials are randomly paired.

[0090] Tinnitus degree = AS response amplitude to stimulation with gaps / AS response amplitude to stimulation without gaps × 100%

[0091] 2.3 Statistical processing of experimental data

[0092] SPSS 22.0 software was used to perform statistical analysis on the data. The measurement data were expressed as (x±s). The normal distribution of each group and the homogeneity of variance between groups were tested first. After the normal distribution and the homogeneity of variance test were met, the t test was used between groups, and the one-way variance test was used for comparison between multiple groups. P<0.05 was considered statistically significant.

[0093] 3. Results and Conclusions

[0094] 3.1 Effect of the Chinese medicine composition of the present invention on the amplitude of AS response in mice

[0095] Compared with the model group, the AS response amplitude of mice in each drug-treated group was significantly reduced, and the difference was statistically significant (P<0.01), indicating that the Chinese medicine composition of the present invention has a good effect in preventing tinnitus.

[0096] Table 1 Comparison of the changes in the AS response amplitude of mice in each group ( n=10)

[0097]

[0098] Note: Compared with the blank group, @ P<0.05, * P < 0.01;

[0099] Compared with the model group, △ P<0.05, # P<0.01.

[0100] 2. The therapeutic effect of the Chinese medicine composition of the present invention on tinnitus rats.

[0101] 1 Materials

[0102] 1.1 Animals:

[0103] Wistar rats, weighing 180–220 g, with experimental animal license number: SYXK(Lu)2018 0008, were provided by Lunan Pharmaceutical Group Co., Ltd. and were adaptively fed for one week before the experiment.

[0104] 1.2 Drugs and reagents

[0105] 1.2.1 Drugs

[0106] Shouhui Tongbian Capsules (National Medicine Standard Z20150041) are available on the market and are produced by Lunan Houpu Pharmaceutical Co., Ltd.

[0107] Example 2 Capsules obtained

[0108] 1.2.3 Dosage in rats

[0109] Shouhui Tongbian Capsule: 0.378g / kg (high dose), 0.189g / kg (medium dose), 0.0945g / kg (low dose);

[0110] Example 2 capsule: 0.189 g / kg;

[0111] 2. Experimental Method

[0112] 2.1 Grouping, modeling and drug administration

[0113] The rats were deprived of water until their body weight dropped to 80% of their original body weight and then the conditioned reflex of "background noise stops - water intake decreases" was performed.

[0114] 60 rats were randomly divided into a blank group, a model group, three dose groups of Shouhui Tongbian Capsule (high, medium and low), and Example 2 group, with 10 rats in each group.

[0115] The specific operations are as follows:

[0116] Rats were placed in a soundproof room with background white noise for drinking water training. When the background white noise appeared at the 5th, 10th, 15th, 20th, and 25th minutes and stopped for 1 minute, the animals were given electric shocks from the drinking spouts when they licked the water. Each rat was trained once a day for 30 minutes. The conditioned stimulus during the training was the cessation of the background white noise, which appeared at the 5th, 10th, 15th, 20th, and 25th minutes of the training, and lasted for 1 minute each time, gradually forming a conditioned reflex of "sound appears-drinking starts, sound disappears-drinking stops". When the conditioned reflex is formed, the training stops and the conditioned reflex enters the extinction period.

[0117] After the animals formed a stable conditioned reflex, before training every day, the model group, the three dose groups of Shouhui Tongbian Capsules, and the Example 2 group were intraperitoneally injected with sodium salicylate solution, and the blank group was intraperitoneally injected with an equal amount of normal saline; in addition, the three dose groups of Shouhui Tongbian Capsules and the Example 2 group were gavaged with corresponding drugs, and the blank group and the model group were gavaged with an equal amount of normal saline. When the conditioned stimulus appeared, the unconditioned stimulus, i.e., electric shock, was no longer given, and the extinction of the conditioned reflex of each group of animals was observed, and its extinction time was recorded.

[0118] 2.2 Statistical processing of experimental data

[0119] SPSS 22.0 software was used to analyze the data. The normal distribution of each group and the homogeneity of variance test between groups were first tested. After the normal distribution and the homogeneity of variance test were met, the t test was used between groups, and the one-way variance test was used for comparison between multiple groups. P < 0.05 was considered statistically significant.

[0120] 3. Results and Conclusions

[0121] Compared with the blank group, the extinction period (i.e., the time for the conditioned reflex of "sound appearance-drinking start, sound disappearance-drinking stop" to disappear during the tinnitus modeling period) of the model group rats was significantly shortened (P<0.01); compared with the model group, the extinction period of the rats in each drug-treated group was prolonged (P<0.01). This indicates that the Chinese medicine composition of the present invention has a significant therapeutic effect on tinnitus.

[0122] Table 2 Comparison of extinction period of rats in each group ( n=10)

[0123]

[0124] Note: Compared with the blank group, @ P<0.05, * P < 0.01;

[0125] Compared with the model group, △ P<0.05, # P<0.01.

Claims

1. Use of a Chinese medicine composition in preparing a drug for preventing, treating or improving tinnitus, wherein: The Chinese medicine composition is composed of the following raw materials: 25-400 parts by weight of Polygonum multiflorum 30-500 parts by weight of Cassia seed 30-600 parts by weight of Aloe vera 30-150 parts by weight of wolfberry 30-150 parts by weight of donkey hide gelatin 20-100 parts by weight of ginseng Fructus Aurantii Immaturus 50-200 parts by weight, Atractylodes macrocephala 20-100 parts by weight.

2. The use according to claim 1, characterized in that The Chinese medicine composition is composed of the following raw materials: 60-150 parts by weight of Polygonum multiflorum 80-180 parts by weight of Cassia seed 100-200 parts by weight of Aloe vera 30-100 parts by weight of wolfberry 30-100 parts by weight of donkey hide gelatin 20-80 parts by weight of ginseng Fructus Aurantii Immaturus 80-150 parts by weight, Atractylodes macrocephala 20-80 parts by weight.

3. The use according to claim 2, characterized in that The Chinese medicine composition is composed of the following raw materials: 80-120 parts by weight of Polygonum multiflorum 100-150 parts by weight of Cassia seed 120-160 parts by weight of Aloe vera 50-80 parts by weight of wolfberry 40-80 parts by weight of donkey hide gelatin 20-50 parts by weight of ginseng 80-120 parts by weight of Citrus aurantium and 30-50 parts by weight of Atractylodes macrocephala.

4. The use according to any one of claims 1 to 3, characterized in that The Chinese medicine composition can be prepared into a clinically acceptable dosage form alone or after adding pharmaceutically acceptable excipients.

5. The use according to claim 4, characterized in that The clinically acceptable dosage form is capsule, tablet, pill, granule or oral liquid preparation.

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