A pharmaceutical composition for weight loss, its application and preparation

Abstract

The present invention discloses a pharmaceutical composition for weight loss, its application and preparation, belonging to the technical field of pharmaceuticals. The pharmaceutical composition is composed of senna leaf, polyporus umbellatus, lotus leaf and hawthorn. The senna leaf is the fermented senna leaf after being fermented by monascus enzyme. The application is the application of the pharmaceutical composition in the preparation of weight loss preparations. The senna leaf prepared by the fermentation treatment of monascus in the present invention can reduce the damage to liver cells and improve the safety of the drug. At the same time, the pharmaceutical composition of the present invention is compounded with four components of fermented senna leaf, polyporus umbellatus, lotus leaf and hawthorn, and produces unexpected technical effects in terms of weight loss. Applying the pharmaceutical composition and its preparation can effectively reduce weight and lipid, and has good safety, no toxic and side effects, and can be used for a long time.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical compositions, and more particularly to a pharmaceutical composition for weight loss, its applications and preparations. Background Art

[0002] Obesity is a common group of metabolic syndromes. When the calories ingested by the human body are more than the calories consumed, the excess calories are stored in the body in the form of fat, and when the amount exceeds the normal physiological requirement and reaches a certain value, it evolves into obesity.

[0003] Obesity is divided into two major categories: simple obesity and secondary obesity. Generally, the obesity referred to is simple obesity, that is, when the weight exceeds 20% of the standard weight, it can be called obesity. Obesity not only affects work, life and appearance, but also has certain harm to health. Obesity is currently the third greatest enemy threatening human health after cardiovascular and cerebrovascular diseases and cancer. Obese people are prone to hypertension, coronary heart disease, fatty liver, diabetes, hyperlipidemia, gout and cholelithiasis, etc. Through clinical tests, the vast majority of simple obesity patients have endocrine disorders, especially problems such as hyperinsulinemia, abnormal glucose tolerance test, disorder of sex hormone levels, high adrenal cortical hormone, and increased leptin.

[0004] Currently, there are mainly two categories of weight loss drugs on the market, pancreatic lipase inhibitors and appetite suppressants that act on the central nervous system. Appetite suppressants are restricted from use due to their potential to cause adverse nervous system reactions. Orlistat, a pancreatic lipase inhibitor, loses weight by inhibiting the activity of pancreatic lipase and thus inhibiting the breakdown and absorption of fat in food. However, it has safety uncertainties such as potential liver function damage.

[0005] CN103623300A discloses a weight-loss traditional Chinese medicine, which is prepared from the following raw materials in parts by weight: 10-20 of cassia seed, 10-20 of hawthorn, 5-10 of glabrous greenbrier rhizome, 5-15 of wolfberry fruit, 5-10 of chrysanthemum, 5-10 of senna leaf, 12-20 of dried tangerine peel, 5-10 of schisandra chinensis, 3-8 of houttuynia cordata, 5-15 of codonopsis pilosula, 5-10 of bupleurum root, 10-20 of barley, and 10-20 of aloe. This invention has the effect of weight loss; CN104189631A discloses a traditional Chinese medicine composition with the effects of weight loss and lipid reduction, which is prepared from the following raw materials, all in parts by weight: 10-25 parts of codonopsis pilosula, 4-30 parts of salvia miltiorrhiza, 10-30 parts of fleece-flower root, 9-5 parts of kudzu root, 8-20 parts of scutellaria baicalensis, 10-40 parts of hawthorn, 5-30 parts of oriental waterplantain rhizome, 5-30 parts of cassia seed, 8-25 parts of poria cocos, 8-25 parts of lotus stem, 8-30 parts of coix seed, 4-20 parts of gardenia fruit, 1-5 parts of senna leaf, 3-15 parts of raw pu-erh tea leaves, and 3-15 parts of ripe pu-erh tea leaves. This invention has good effects of weight loss and lipid reduction, no any toxic and side effects, good taste, no rebound after use, and can enhance resistance; CN112107664A discloses a traditional Chinese medicine composition for reducing body weight, its preparation method and application, which is mainly composed of 2-6 parts of poria cocos, 1-4 parts of dried tangerine peel, 1-4 parts of cardamom, 2-8 parts of coix seed, 1-5 parts of apricot kernel, 1-5 parts of patchouli, 1.5-4.5 parts of oriental waterplantain rhizome, 0.5-2.5 parts of senna leaf, 2-6 parts of cassia seed, and 2-4 parts of lotus leaf, and is prepared by decocting and extracting ten raw material medicines in total. It can be used to prepare various preparations, and also has the effect of reducing people's body weight in the application of preparing drugs for treating obesity.

[0006] Senna leaf, also known as cathartic leaf, acts on both the large intestine and the small intestine, can accelerate the peristalsis of the large intestine, cause defecation in a short time, and has a significant therapeutic effect. However, because constipation is a long-term and recurrent disease, long-term use is likely to lead to drug dependence and liver damage (Research on liver damage caused by long-term abuse of senna leaf in the treatment of constipation, Chinese Journal of Drug Abuse Prevention and Treatment [J], Cui Liying et al., Vol. 21, No. 3, 2021, pp. 404-408). Regarding the toxicity of anthraquinone laxatives, there is currently widespread concern. Although the relative abundance of anthraquinone compounds in senna leaf is not high, some anthraquinone monomers, such as emodin and rhein, have strong liver and kidney toxicity. As a widely used Chinese herbal medicine worldwide, senna leaf has a wide range of applications, yet its potential biological toxicity limits its scope of use.

[0007] Pei Xiaomei found in the study of senna safety evaluation and the process of anthraquinone degradation of senna by red yeast fermentation that fermenting senna with high red yeast pigment and low citrinin output can reduce the content of anthraquinone compounds such as rhein and aloe-emodin in senna, thereby improving the safety of senna (Study on the Safety Evaluation of Senna and the Process of Anthraquinone Degradation of Senna by Red Yeast Fermentation, Full-time Professional Master's Thesis of Jiangnan University, June 2022). However, anthraquinone and its derivatives are the main active substances that play a laxative role. While reducing anthraquinone compounds during the fermentation process, this study also reduced the weight loss effect of senna. How to improve the safety of senna while developing an effective weight loss drug composition is a technical problem that needs to be solved urgently. Summary of the invention

[0008] The object of the present invention is to provide a pharmaceutical composition for weight loss and its application and preparation. The pharmaceutical composition of the present invention is compounded with four ingredients of fermented senna leaves, Poria cocos, lotus leaves and hawthorn, and produces unexpected technical effects in weight loss. The application of the pharmaceutical composition and its preparation can effectively reduce weight and reduce blood lipids, and has good safety, no toxic side effects, and can be used for a long time.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] A medicine composition for weight loss, comprising senna leaves, umbellate polyporus, lotus leaves and hawthorn.

[0011] Wherein, the senna leaf is fermented senna leaf treated with monascus enzyme fermentation.

[0012] Specifically, the fermentation method of senna comprises the following steps:

[0013] (1) crushing senna leaves to obtain senna leaf powder;

[0014] (2) Spraying bacterial liquid onto the surface of senna leaf powder, fermenting the powder, and drying the fermented residue to obtain fermented senna leaf.

[0015] Preferably, the particle size of the senna leaf powder in step (1) is 0.5-1 mm.

[0016] Preferably, the mass concentration of Monascus in the bacterial solution in step (2) is 1-3%, and the number of viable bacteria is 5×10 8 cfu / ml.

[0017] The Monascus described in the present invention is a conventional commercially available strain, such as Monascus TS290799.

[0018] Preferably, the amount of the bacterial solution in step (2) is 10-15% by weight of the senna leaf powder; more preferably 12-14%; most preferably 13%.

[0019] Preferably, the fermentation in step (2) is carried out at 25 - 30 °C for 48 - 72 h.

[0020] Preferably, the pharmaceutical composition for weight loss is composed of the following components in parts by weight: 1 - 5 parts of senna leaf, 3 - 8 parts of polyporus umbellatus, 10 - 15 parts of lotus leaf, and 10 - 30 parts of hawthorn.

[0021] More preferably, the pharmaceutical composition for weight loss is composed of the following components in parts by weight: 1.5 - 4.5 parts of senna leaf, 3.5 - 7 parts of polyporus umbellatus, 11 - 14 parts of lotus leaf, and 12 - 25 parts of hawthorn.

[0022] Most preferably, the pharmaceutical composition for weight loss is composed of the following components in parts by weight: 3 parts of senna leaf, 4.5 parts of polyporus umbellatus, 12 parts of lotus leaf, and 20 parts of hawthorn.

[0023] The present invention also provides a preparation method of the above - mentioned pharmaceutical composition, comprising the following steps:

[0024] S1. Mix the formula - amount of senna leaf, polyporus umbellatus, lotus leaf, and hawthorn, add water for decoction, and obtain a filtrate;

[0025] S2. Concentrate and dry the filtrate to obtain the pharmaceutical composition.

[0026] Preferably, the adding water for decoction in step S1 is: adding 10 - 15 times the total formula amount of water for decoction 1 - 3 times, and the decoction time for each time is 1 - 2 h.

[0027] The present invention also provides the application of the above - mentioned pharmaceutical composition for weight loss in the preparation of weight - loss preparations.

[0028] The present invention also provides a weight - loss preparation, comprising the above - mentioned pharmaceutical composition for weight loss.

[0029] Preferably, the weight - loss preparation is a granule, pill, tablet, powder, ointment, oral liquid, suspension, or capsule.

[0030] The beneficial effects of the present invention are as follows:

[0031] (1) Compared with the traditional Chinese medicine composition prepared by using unfermented senna leaf, the cell survival rate of the traditional Chinese medicine composition of the present invention is higher. It shows that the senna leaf prepared by the fermentation treatment of Monascus purpureus in the present invention can reduce the damage to liver cells and improve the safety of the drug.

[0032] (2) The fermented senna leaf of the present invention is compounded with four components of polyporus umbellatus, lotus leaf, and hawthorn, and produces unexpected technical effects in weight loss.

[0033] (3) Compared with the prior art, the pharmaceutical composition and its preparation of the present invention can effectively reduce weight and lipid, have good safety, no toxic and side effects, and can be used for a long time. Detailed implementation manners

[0034] The following description of the embodiments is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art of this technology, without departing from the principle of the present invention, several improvements and modifications can still be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention. The following description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but can be applied to a wider range consistent with the principles and novel features disclosed herein.

[0035] Example 1 Pharmaceutical composition for weight loss

[0036] The pharmaceutical composition is composed of the following components in parts by weight: 3 parts of senna leaf, 4.5 parts of polyporus umbellatus, 12 parts of lotus leaf, and 20 parts of hawthorn.

[0037] Among them, the senna leaf is the fermented senna leaf after being fermented by monascus enzyme. The specific fermentation method is as follows:

[0038] (1) Crush the senna leaf to obtain senna leaf powder with a particle size of 0.5 - 1 mm;

[0039] (2) Spray the bacterial liquid on the surface of the senna leaf powder, ferment at 28 °C for 48 h, and dry the fermented residue to obtain the fermented senna leaf.

[0040] The dosage of the bacterial liquid is 13% of the weight of the senna leaf powder; the mass concentration of monascus (TS290799, purchased from Testo Biotechnology) in the bacterial liquid is 1%, and the viable count is 5×10 8 cfu / ml.

[0041] The preparation method of the pharmaceutical composition is as follows:

[0042] S1. Mix the formula amounts of senna leaf, polyporus umbellatus, lotus leaf, and hawthorn, add 15 times the amount of water and decoct for 2 h to obtain a filtrate;

[0043] S2. Concentrate and dry the filtrate to obtain a pharmaceutical composition with a water content of less than 8%.

[0044] Example 2 Pharmaceutical composition for weight loss

[0045] The pharmaceutical composition consists of the following components in parts by weight: 1 part of senna leaf, 3 parts of polyporus umbellatus, 10 parts of lotus leaf, and 10 parts of hawthorn.

[0046] Among them, the senna leaf is the fermented senna leaf after being fermented by monascus enzyme, and the specific fermentation method is as follows:

[0047] (1) Crush the senna leaf to obtain senna leaf powder with a particle size of 0.5 - 1 mm;

[0048] (2) Spray the bacterial liquid on the surface of the senna leaf powder, ferment at 28 °C for 48 h, and dry the fermented residue to obtain the fermented senna leaf.

[0049] The dosage of the bacterial liquid is 13% of the weight of the senna leaf powder; the mass concentration of monascus (TS290799, purchased from TestoBio) in the bacterial liquid is 1%, and the viable bacteria count is 5×10 8 cfu / ml.

[0050] The preparation method of the pharmaceutical composition is the same as that of Example 1.

[0051] Example 3 Pharmaceutical composition for weight loss

[0052] The pharmaceutical composition consists of the following components in parts by weight: 5 parts of senna leaf, 8 parts of polyporus umbellatus, 15 parts of lotus leaf, and 30 parts of hawthorn.

[0053] Among them, the senna leaf is the fermented senna leaf after being fermented by monascus enzyme, and the specific fermentation method is as follows:

[0054] (1) Crush the senna leaf to obtain senna leaf powder with a particle size of 0.5 - 1 mm;

[0055] (2) Spray the bacterial liquid on the surface of the senna leaf powder, ferment at 28 °C for 48 h, and dry the fermented residue to obtain the fermented senna leaf.

[0056] The dosage of the bacterial liquid is 13% of the weight of the senna leaf powder; the mass concentration of monascus (TS290799, purchased from TestoBio) in the bacterial liquid is 1%, and the viable bacteria count is 5×10 8 cfu / ml.

[0057] The preparation method of the pharmaceutical composition is the same as that of Example 1.

[0058] Comparative Example 1 Pharmaceutical composition for weight loss

[0059] The difference between this comparative example and Example 1 is only that: the senna leaf is not fermented by monascus enzyme.

[0060] The preparation method of the pharmaceutical composition is the same as that of Example 1.

[0061] Drug composition for weight loss in Comparative Example 2

[0062] The difference between this comparative example and Example 1 is only that: the drug composition does not contain Polyporus umbellatus.

[0063] Specifically, the composition of the drug composition is: 3 parts of Folium Sennae, 12 parts of Folium Nelumbinis and 20 parts of Fructus Crataegi. Among them, Folium Sennae is fermented Folium Sennae after being treated with Monascus enzyme. The specific fermentation method is as follows:

[0064] (1) Crush Folium Sennae to obtain Folium Sennae powder with a particle size of 0.5 - 1 mm;

[0065] (2) Spray the bacterial liquid on the surface of the Folium Sennae powder, ferment at 28 °C for 48 h, dry the fermented residue to obtain fermented Folium Sennae,

[0066] The dosage of the bacterial liquid is 13% of the weight of the Folium Sennae powder; the mass concentration of Monascus purpureus (TS290799, purchased from Testo Biotechnology) in the bacterial liquid is 1%, and the viable count is 5×10 8 cfu / ml.

[0067] The preparation method of the drug composition is as follows:

[0068] S1. Mix the formulated amounts of Folium Sennae, Folium Nelumbinis and Fructus Crataegi, add 15 times the amount of water and boil for 2 h to obtain a filtrate;

[0069] S2. Concentrate and dry the filtrate to obtain a drug composition with a water content of less than 8%.

[0070] Drug composition for weight loss in Comparative Example 3

[0071] The difference between this comparative example and Example 1 is only that: the drug is only Polyporus umbellatus.

[0072] The preparation method of the drug composition is as follows:

[0073] S1. Add the formulated amount of Polyporus umbellatus, add 15 times the amount of water and boil for 2 h to obtain a filtrate;

[0074] S2. Concentrate and dry the filtrate to obtain a drug composition with a water content of less than 8%.

[0075] Drug composition for weight loss in Comparative Example 4

[0076] The difference between this comparative example and Example 1 is only that: the dosages of each component in the drug composition are different, specifically:

[0077] 3 parts of Folium Sennae, 12 parts of Polyporus umbellatus, 20 parts of Folium Nelumbinis and 4.5 parts of Fructus Crataegi.

[0078] The fermentation process of Folium Sennae is the same as that in Example 1;

[0079] The preparation method of the pharmaceutical composition is implemented simultaneously with Example 1.

[0080] I. Safety evaluation

[0081] Sample solution preparation: Respectively take the pharmaceutical compositions prepared in Examples 1-3 and Comparative Example 1, add DMSO, and prepare a sample solution with a concentration of 1000 mg / L.

[0082] According to 1×10 4 HepG2.2.15 cells (purchased from Wuxi Xinrun) / ml, inoculate into a 96-well plate, the inoculation amount is 100 μL / well, after culturing at 37°C for 24 h, aspirate the culture medium, wash once with PBS, set experimental wells, control wells and blank wells. Among them, add 100 μL of culture medium containing sample solution with different concentrations to each experimental well, add an equal amount of culture medium to the control well, and add an equal amount of PBS to the blank well. After culturing at 37°C for 48 h, aspirate the culture medium, add 100 μL of 5 g / L MTT to each well, continue to culture for 4 h, aspirate the supernatant, add 100 μL of DMSO to each well, shake for 10 min, and measure the absorbance value at 450 nm for each well.

[0083] Cell survival rate = (OD of experimental well - OD of blank well) * 100% / (OD of control well - OD of blank well).

[0084] The results are shown in Table 1.

[0085] Table 1

[0086]

[0087] As can be seen from the above table, compared with the traditional Chinese medicine composition prepared from unfermented senna leaves, the cell survival rate of the traditional Chinese medicine composition of the present invention is higher. It shows that the senna leaves prepared by the fermentation treatment of Monascus purpureus in the present invention can reduce the damage to liver cells and improve the safety of the drug.

[0088] II. Evaluation of weight loss efficacy

[0089] Select male SD rats with a body weight of 180-200 g (purchased from Changchun Yisi Experimental Animal Technology Co., Ltd.). After 3 days of adaptive feeding, randomly divide them into 2 groups according to body weight. 8 are used as the normal control group, fed with basal diet, and the rest are the high-fat nutrition diet group, fed with high-fat nutrition diet (composed of 70% basal diet, 10% egg yolk powder, 5% cholesterol and 15% egg yolk powder). After 30 days of feeding, when the average body weight of the rats in the high-fat nutrition diet group is significantly higher than that of the normal control group (P < 0.05), the obesity rat model is successfully established.

[0090] The successfully modeled obese rats were randomly divided into a model group and a drug administration group (specifically: Example 1-3 groups and Comparative Example 1-4 groups), with 8 rats in each group. The drug administration group was intragastrically administered the drug compositions prepared in the corresponding examples and comparative examples, with a dosage of 60 mg / kg once a day. The model group and the normal control group were intragastrically administered an equal dose of normal saline, and intragastric administration was continued for 4 weeks. During the experiment, the normal control group was fed a basal diet, and the other groups were fed a high-fat diet. All rats in all groups had normal drinking water and exercise, and the rats were weighed at the 4th week after intragastric administration. At the end of the experiment, the body weight of the rats was measured. After anesthesia with intraperitoneal injection of 10% chloral hydrate (3.5 ml / kg), the body fat (testicular and perirenal fat pads) was taken out by laparotomy and weighed, and the fat-body ratio was calculated. Among them, the calculation formula of the fat-body ratio is: fat-body ratio % = total body fat * 100 / body weight.

[0091] One-way analysis of variance was performed using SPSS 16.0 software, and the processed data were expressed as mean ± standard deviation ( ).

[0092] The results are shown in Table 2 - Table 3.

[0093] Table 2 Body weights of rats in different groups ( )

[0094]

[0095] Note: Different letters represent significant differences in data between groups (P < 0.05).

[0096] The results in Table 2 show that compared with the normal control group, there were significant differences in the initial body weights of the rats in each group, indicating that the modeling of obese rats was successful. And except for the normal control group, there were no significant differences in the initial body weights of the rats in each group.

[0097] After continuous feeding for 4 weeks, compared with the model group, except for the Comparative Example 2-4 groups, there were significant differences in the weight reduction of the rats in other groups (P < 0.05), indicating that the drug composition of the present invention can reduce the weight gain of obese rats and has a weight loss effect.

[0098] At the same time, by comparing the model group and the Comparative Example 2-4 groups, it can be found that compared with the model group, there were no significant differences in the weight reduction of the rats in the Comparative Example 2-4 groups (P > 0.05), indicating that the drug compositions provided by Comparative Examples 2-4 cannot reduce the weight gain of obese rats and thus do not have a weight loss effect.

[0099] From the Example 1 group and the Comparative Example 4 group, it can be seen that the combination of specific dosages of senna leaf, polyporus umbellatus, lotus leaf and hawthorn in the present invention can achieve a good weight loss effect and obtain unexpected technical effects.

[0100] Table 3 shows the total body fat weight and fat body ratio of rats in different groups in the fourth week ( ).

[0101]

[0102] Note: Different letters represent significant differences in data between groups (P < 0.05).

[0103] The results in Table 3 show that after 4 weeks of gavage, compared with the normal control group, the total body fat amount and fat body ratio of rats in the model group increased significantly, indicating that there was obvious fat accumulation in obese rats.

[0104] Compared with the model group, except for groups 2 - 4 of the comparative example, the total body fat amount and fat body ratio of rats in other groups decreased significantly (P < 0.05), indicating that the pharmaceutical composition of the present invention has the effect of reducing fat accumulation.

[0105] Meanwhile, by comparing the model group and groups 2 - 4 of the comparative example, it can be found that compared with the model group, the total body fat amount and fat body ratio of rats in groups 2 - 4 of the comparative example did not decrease significantly (P > 0.05), indicating that the pharmaceutical compositions provided in the comparative examples 2 - 4 do not have the effect of reducing fat accumulation.

[0106] In summary, in the technical solution claimed in the present invention, polyporus does not have an obvious effect of reducing fat accumulation, while the combination of specific dosages of senna leaf, lotus leaf, hawthorn and polyporus in the present invention can achieve a better effect of reducing fat accumulation, which is unexpected.

[0107] The above is a further description of the present invention in combination with specific embodiments, but these embodiments are merely exemplary and do not constitute any limitation to the scope of the present invention. Those skilled in the art should understand that without departing from the spirit and scope of the present invention, modifications or substitutions can be made to the details and forms of the technical solution of the present invention, but these modifications and substitutions all fall within the protection scope of the present invention.

Claims

1. A pharmaceutical composition for weight loss, characterized in that, The invention is prepared from the following components in parts by weight: 1-5 parts of senna leaves, 3-8 parts of Poria cocos, 10-15 parts of lotus leaves and 10-30 parts of hawthorn; the senna leaves are fermented senna leaves fermented with monascus enzyme; the fermentation method of the fermented senna leaves comprises the following steps: (1) crushing senna leaves to obtain senna leaf powder; (2) spraying bacterial liquid on the surface of senna leaf powder, fermenting, and drying the fermented residue to obtain fermented senna leaf; The mass concentration of Monascus in the bacterial solution in step (2) is 1-3%; the amount of the bacterial solution used is 10-15% of the weight of the senna leaf powder; and the fermentation in step (2) is carried out at 25-30° C. for 48-72 hours.

2. The pharmaceutical composition according to claim 1, wherein The invention is prepared from the following components in parts by weight: 3 parts of senna leaves, 4.5 parts of polyporus, 12 parts of lotus leaves and 20 parts of hawthorn.

3. The preparation method of the pharmaceutical composition according to any one of claims 1-2, characterized in that, The following steps are involved: S1, mixing the formulated amounts of senna leaves, umbellate, lotus leaves and hawthorn, adding water and boiling to obtain a filtrate; S2. Concentrate and dry the filtrate to obtain a pharmaceutical composition.

4. Use of the pharmaceutical composition for weight loss according to any one of claims 1 to 2 in the preparation of a weight loss preparation.

5. A weight loss preparation, characterized in that, A pharmaceutical composition for weight loss comprising any one of claims 1 to 2.

6. The weight loss preparation according to claim 5, characterized in that, The weight loss preparation is in the form of granules, pills, tablets, pastes, oral liquids, suspensions or capsules.

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