CN114159480A - Composition with weight-losing effect and preparation method and application thereof - Google Patents
Composition with weight-losing effect and preparation method and application thereof Download PDFInfo
- Publication number
- CN114159480A CN114159480A CN202210060434.5A CN202210060434A CN114159480A CN 114159480 A CN114159480 A CN 114159480A CN 202210060434 A CN202210060434 A CN 202210060434A CN 114159480 A CN114159480 A CN 114159480A
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- Prior art keywords
- inonotus obliquus
- orlistat
- composition
- extract
- precipitate
- Prior art date
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- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention belongs to the technical field of biological medicines, and particularly relates to a composition with a weight-losing effect, which at least comprises orlistat and inonotus obliquus extracts. The composition provided by the invention can be used for preventing or treating weight loss and/or lipid lowering, and a large number of experiments prove that the composition provided by the invention has quite beneficial effects on reducing weight, reducing fat accumulation and inhibiting fat absorption, the weight loss effect is obviously better than orlistat, and more importantly, the whole medicament shows lower adverse reaction (obviously lower than that of the orlistat used alone).
Description
Technical Field
The invention belongs to the technical field of biological medicines. More particularly, relates to a composition with weight-losing effect, a preparation method and application thereof.
Background
Obesity is a chronic endocrine metabolic disease caused by a series of eating regulation and energy metabolism disorders caused by specific biochemical factors, energy intake is more than consumed and exists in the body in the form of fat, and the body constitution is very much. Generally, a Body Mass Index (BMI) of not less than 25 is overweight, and a BMI of not less than 30 is obese. Obesity is a risk factor for various chronic diseases, such as diabetes, hyperlipidemia, insulin resistance, apnea sleep syndrome, dyspnea, restless anxiety, coronary heart disease, hypertension, reproductive hormone abnormality, polycystic ovary syndrome, etc., and thus, there is a great need for the treatment of obesity.
The current methods for eliminating obesity include diet control, exercise therapy, drug therapy, and the like. When diet control and exercise therapy are difficult to adhere to or the body has pathological factors of polyphagia, a means of medicine auxiliary treatment is necessary. The current drugs for obesity are broadly divided into two main groups: chemical medicines, Chinese medicines and compound medicines. The treatment mechanism of the western medicines mainly comprises appetite suppressing medicines (such as sibutramine, amphetamine and fenfluramine), energy metabolism increasing medicines (ephedrine and thyroid tablet), medicines for inhibiting intestinal digestion and absorption (orlistat) and other medicines for treating obesity (obesity gene products and insulin sensitizers), wherein the sibutramine and orlistat are most widely applied.
Orlistat (orlistat) is a long-acting and potent specific gastrointestinal lipase inhibitor that exerts a therapeutic effect by inactivating enzymes through the formation of covalent bonds with the active serine sites of gastric lipase in the stomach and pancreatic lipase in the small intestine lumen. The inactivated enzymes are unable to hydrolyze fats (primarily triglycerides) in the food to absorbable free fatty acids and monoacylglycerols. Undigested triglycerides are not absorbed by the body, thereby reducing caloric intake and controlling body weight. Compared with other appetite-forbidden antiobesity drugs, orlistat does not affect appetite and does not act on the central nervous system, so that orlistat has higher safety, and the chemical structural formula of the orlistat is shown as follows:
however, adverse reactions of gastrointestinal tract caused by long-term use of orlistat are common, and because orlistat acts on the digestive tract, most of treatment patients are easy to have oily spots in stool, increased gastrointestinal gas discharge, urgent stool, fatty (oily) stool, fatty diarrhea, increased stool frequency, fecal incontinence and the like after long-term use. Therefore, the biggest problem of the application of orlistat medicines at present is how to reduce the adverse gastrointestinal reactions caused by orlistat medicines.
Fuscoporia obliqua (Fuscoporia obliqua) belongs to Aphyllum obliqua of Polyporaceae, contains various components mainly including steroid, triterpene, polyphenol and polysaccharide, and has effects in resisting tumor, resisting oxidation, reducing blood glucose, resisting inflammation, resisting virus and enhancing immunityPharmacological activity. For example, Yangming[1]The reports show that the inonotus obliquus polyphenol has very obvious effect of removing DPPH free radicals, hydroxyl free radicals and superoxide anion free radicals and has an antioxidant effect; cui Y[2]And reports that triterpenes and steroids compounds in other main components of the inonotus obliquus also have certain antioxidant activity, and polysaccharide has the lowest antioxidant activity. However, at present, no report that the inonotus obliquus extract is used for losing weight together with orlistat and assisting in reducing gastrointestinal adverse reactions of orlistat is found.
[1] Yangming, Pengyonggang, Zhang hongli, Chen Bao bin, Tanzing, Inonotus obliquus polyphenol extraction and antioxidant activity research [ J ]. Guangzhou chemical industry, 2019,47(09):115 and 117.
[2]Cui Y，Kim D S，Park K C，Antioxidant effect of Inonotus obliquus，Journal of Ethnopharmacol，2005，96:79-85.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defects and shortcomings of the existing orlistat weight-reducing drugs and provides a weight-reducing composition taking an inonotus obliquus extract and orlistat as main active ingredients. Particularly, the technical scheme provided by the invention can obviously reduce the body weight of the obese rat and reduce the accumulation of fat, and has excellent weight-losing effect.
The invention aims to provide a composition with weight-losing effect, which at least comprises orlistat and inonotus obliquus extracts.
Further, in the composition, the mass ratio of the inonotus obliquus extract to orlistat is 6.2:1-12:1, preferably 7:1-12:1, more preferably 8:1-12:1, such as 6.2:1, 7:1, 7.5:1, 8:1, 8.5:1 and any value between the above ratios.
The "inonotus obliquus extract" referred to above is a mixture of an aqueous extract and an ethanol extract of inonotus obliquus, because most of the steroid compounds, polysaccharides and polyphenol compounds in inonotus obliquus can be extracted by aqueous extraction and ethanol extraction in order to enrich more active ingredients in inonotus obliquus at first. However, the inventor of the present invention unexpectedly found in research that the use of the inonotus obliquus extract (water extract + alcohol extract) and orlistat together is very effective in reducing the gastrointestinal adverse reaction problem caused by orlistat, although the drug as a whole shows lower adverse reaction (significantly lower than orlistat alone), and particularly the increase in stool oily spots and gastrointestinal gas discharge caused by orlistat is significantly improved. However, the further research on the weight-losing activity of the medicament shows that the whole medicament shows less ideal effects of reducing fat and weight, even lower than the effects of singly using orlistat.
The inventors further studied the technical scheme, in order to study how to reduce the negative effect of inonotus obliquus extract on orlistat weight-reducing effect without sacrificing or even improving the weight-reducing effect of orlistat. The inventor speculates that the effect may be antagonistic interaction between a certain component in the inonotus obliquus extract and orlistat in reducing body weight, and through a great deal of research, the inventors surprisingly found that the negative effect of the inonotus obliquus extract on the weight-reducing effect of orlistat is mainly derived from steroid compounds in the inonotus obliquus extract, because the test results show that when the steroid compounds are less or even not contained, the medicament has a remarkable weight-reducing promoting effect as a whole, and meanwhile, gastrointestinal adverse reactions caused by orlistat are also remarkably reduced.
In some embodiments, the inonotus obliquus extract contains no or little inonotus obliquus steroids. Tests prove that the existence of the steroid compound has adverse effect on the weight-losing effect of orlistat, and after the inonotus obliquus extract containing the steroid compound and orlistat are used together for 7 weeks, the weight gain of rats has a certain difference compared with that of a group which is singly administered with orlistat.
Further, the steroid compounds of the inonotus obliquus comprise lanosterol, inonotus obliquus alcohol and ergosterol. The steroid compounds in the inonotus obliquus are identified by Lanosterol, Ergosterol, peroxyergosterol, Inotodiol, fungosterol, inotsuoxoiol A, inotsudiol A, 3 beta-hydroxyanosta-8, 24-dien-21-al, etc. The contents of lanosterol and inonotus obliquus alcohol are relatively high, and the chemical structural formulas of lanosterol, ergosterol and inonotus obliquus alcohol are respectively shown as follows:
in some embodiments, the inonotus obliquus extract consists essentially of inonotus obliquus polysaccharides and inonotus obliquus polyphenols.
In some embodiments, the method of preparing the inonotus obliquus extract comprises the steps of:
s1, taking the wild sporocarp of the inonotus obliquus, crushing into coarse powder, adding 70-85% of ethanol solution by volume fraction into the coarse powder, performing reflux extraction at the temperature of 80-90 ℃ for 1-3 times, performing 1-3 hours each time, performing reduced pressure filtration, and collecting extraction residues;
s2, adding deionized water into the residue for reflux extraction to obtain a water extract containing the polysaccharide and the polyphenol of the inonotus obliquus; rotary evaporating the water extract to dryness, adding an ethanol solution with the volume fraction of 85-95%, standing overnight, centrifuging, and collecting a precipitate and a supernatant;
s3, removing proteins from the collected precipitate by adopting a Sevag method, then adding ethanol with the volume fraction of 85-95% again, precipitating overnight, centrifuging, collecting the precipitate, washing the precipitate by adopting absolute ethyl alcohol, acetone and petroleum ether in sequence, dissolving the washed precipitate in deionized water, and freeze-drying to obtain a product A;
s4, concentrating the supernatant collected in the step S2 under reduced pressure, slowly adding the concentrated supernatant into a macroporous resin chromatographic column, performing gradient elution by sequentially adopting deionized water and 30-60% volume fraction ethanol solution, collecting ethanol eluate, concentrating under reduced pressure, and drying to obtain a product B;
s5, mixing the product A and the product B to obtain the inonotus obliquus extract.
In some embodiments, step S1 is performed by heating and refluxing with ethanol to remove the steroid compounds in the inonotus obliquus, and during the heating and refluxing extraction, an 80% ethanol solution is preferably added; preferably, the material-liquid ratio is 1: 20-30 m/v, and more preferably 1: 25; in particular, the extraction temperature is preferably 85 ℃ and 90 ℃; the extraction was repeated 3 times, each for 2 h. Most of the steroid compounds in the inonotus obliquus can be removed by the repeated extraction.
In some embodiments, in step S2, the reflux extraction conditions of deionized water are as follows: the ratio of the material to the liquid is 1: 20-30 m/v, preferably 1:22m/v, 1:20m/v and 1:30 m/v; the extraction temperature is 90-100 ℃, preferably 90 ℃, 95 ℃ and 100 ℃; reflux extraction is carried out for 1-3 times, and extraction is preferably carried out for 3 times; each time is 1-2 h, preferably 2 h.
In some embodiments, in the step S2, 85-95% volume fraction ethanol solution is added according to a feed-to-liquid ratio of 1: 1-5 m/v; preferably, the material-liquid ratio is 1:3, 1:4 and 1: 5; the volume fraction of the ethanol solution added is preferably 85%, 90%, 95%.
In some embodiments, the step S3 further comprises a step of separating and purifying inonotus obliquus polysaccharide by using an anion exchange column. More preferably, the anion exchange column is an anion exchange column (DEAE-52).
In some embodiments, the specific isolation and purification steps are: dissolving the product A obtained in the step S3 in deionized water, centrifuging, taking supernatant, performing ultrafiltration, and slowly adding the supernatant into a pretreated anion exchange column; eluting with 0.2M NaCl solution, and collecting eluate.
In some embodiments, the "Sevag method removing proteins" in the step S3 is specifically operated as: dissolving the collected precipitate in deionized water at room temperature; mixing the above solution and chloroform-n-butanol solution (mixed solution at volume ratio of 4: 1) at volume ratio of 4:1, shaking for 30min, and centrifuging; taking the water phase, adding chloroform-n-butanol solution with the same volume, repeating the above process for 3 times, and concentrating.
In some embodiments, in step S4, the dynamic loading method is preferably used for loading, and the loading flow rate is preferably 1-3 times of column volume/h, and more preferably 2.5 times of column volume/h; the volume fraction of the ethanol solution at gradient elution is preferably 30%, 50% or 60%; in gradient elution, each gradient elutes 4 column volumes; during gradient elution, the elution is preferably carried out at the temperature of 30-45 ℃ and under the pressure of 0.02-0.06 MPa; more preferably at 42 ℃ and 0.05 MPa; more preferably, the elution is carried out at 40 ℃ and 0.06 MPa.
The composition can be used for preventing or treating weight loss and/or lipid lowering medicines. In principle, the composition can be prepared in the form of preparations commonly used in pharmacy, including but not limited to: tablets, capsules, granules, when prepared into a specific formulation form, can be prepared by a method commonly used in the field of pharmaceutical preparations.
In addition, when the composition of the present invention is prepared into a specific formulation, it may further include a pharmaceutically acceptable carrier, including but not limited to 1) excipients: citric acid, dicalcium phosphate, starch, sucrose, and the like; 2) adhesive: cellulose and derivatives, starch, gelatin, and the like; 3) disintegrating agent: calcium carbonate, CMC, silicate, sodium carbonate, etc.; 4) wetting agent: glyceryl monostearate and the like; 5) lubricant: talc, magnesium stearate, calcium stearate, and the like.
The invention has the following beneficial effects:
the composition provided by the invention can be used for preventing or treating weight loss and/or lipid lowering, and a large number of experiments prove that the composition provided by the invention has quite beneficial effects on reducing weight, reducing fat accumulation and inhibiting fat absorption, the weight loss effect is obviously better than orlistat, and more importantly, the whole medicament shows lower adverse reaction (obviously lower than that of the orlistat used alone).
Detailed Description
The present invention will be further described by the following examples, however, the scope of the present invention is not limited to the following examples. It will be understood by those skilled in the art that various changes and modifications may be made to the invention without departing from the spirit and scope of the invention.
Example 1 Inonotus obliquus extract preparation (P1)
S1, taking the wild sporocarp of the inonotus obliquus, crushing into coarse powder, adding 80% ethanol solution according to the material-liquid ratio of 1:25m/v, carrying out reflux extraction at 85 ℃ for 3 times, 2 hours each time, carrying out reduced pressure filtration, and collecting extraction residues;
s2, taking the residues, adding deionized water into the residues according to the material-liquid ratio of 1:22m/v for reflux extraction, and performing reflux extraction at 90 ℃ for 3 times, 2 hours each time, so as to obtain a water extract containing the polysaccharide and the polyphenol of the inonotus obliquus; rotary evaporating the water extract to dryness, adding 90% ethanol solution according to the material-liquid ratio of 1:3m/v, standing overnight, centrifuging, and collecting precipitate and supernatant;
s3, dissolving the collected precipitate in deionized water at room temperature; mixing the above solution and chloroform-n-butanol solution (mixed solution at volume ratio of 4: 1) at volume ratio of 4:1, shaking for 30min, and centrifuging; adding chloroform-n-butanol solution into water phase, repeating the above process for 3 times, and concentrating to obtain concentrated solution;
s4, adding 95% ethanol by volume fraction into the concentrated solution according to the proportion of 1:3v/v, precipitating overnight, centrifuging, collecting precipitate, washing the precipitate with absolute ethanol, acetone and petroleum ether in sequence, dissolving the washed precipitate in deionized water, and freeze-drying to obtain the inonotus obliquus crude polysaccharide; dissolving the obtained Fuscoporia obliqua polysaccharide in deionized water, centrifuging, collecting supernatant, ultrafiltering, and slowly adding into pretreated anion exchange column (DEAE-52) chromatographic column; eluting with 0.2M NaCl solution, collecting eluate, concentrating, and freeze drying to obtain product A mainly containing Fuscoporia obliqua polysaccharide;
s5, concentrating the supernatant collected in the step S2 under reduced pressure, slowly adding the concentrated supernatant into a macroporous resin chromatographic column by adopting a dynamic sample loading method, performing gradient elution by sequentially adopting deionized water and 50% volume fraction ethanol solution, collecting ethanol eluent, concentrating under reduced pressure, and drying to obtain a product B mainly containing inonotus obliquus polyphenol; wherein, the sampling flow rate is preferably 2.5 times of the column volume/h, the elution is preferably carried out under the conditions of 42 ℃ and 0.05MPa during the gradient elution, and each gradient elution is 4 times of the column volume;
s6, mixing the product A and the product B to obtain the inonotus obliquus extract.
Example 2 Inonotus obliquus extract preparation (P2)
S1, taking the wild sporocarp of the inonotus obliquus, crushing into coarse powder, adding 70% ethanol solution according to the material-liquid ratio of 1:20m/v, carrying out reflux extraction at 90 ℃ for 3 times, 2 hours each time, carrying out reduced pressure filtration, and collecting extraction residues;
s2, taking the residues, adding deionized water into the residues according to the material-liquid ratio of 1:20m/v for reflux extraction, and performing reflux extraction at 95 ℃ for 3 times, 2 hours each time, so as to obtain a water extract containing the polysaccharide and the polyphenol of the inonotus obliquus; rotary evaporating the water extract to dryness, adding 85% ethanol solution according to the material-liquid ratio of 1:4m/v, standing overnight, centrifuging, and collecting precipitate and supernatant;
s3, dissolving the collected precipitate in deionized water at room temperature; mixing the above solution and chloroform-n-butanol solution (mixed solution at volume ratio of 4: 1) at volume ratio of 4:1, shaking for 30min, and centrifuging; adding chloroform-n-butanol solution into water phase, repeating the above process for 3 times, and concentrating to obtain concentrated solution;
s4, adding 95% ethanol by volume fraction into the concentrated solution according to the ratio of 1:4v/v, precipitating overnight, centrifuging, collecting precipitate, washing the precipitate with absolute ethanol, acetone and petroleum ether in sequence, dissolving the washed precipitate in deionized water, and freeze-drying to obtain the inonotus obliquus crude polysaccharide; dissolving the obtained Fuscoporia obliqua polysaccharide in deionized water, centrifuging, collecting supernatant, ultrafiltering, and slowly adding into pretreated anion exchange column (DEAE-52) chromatographic column; eluting with 0.2M NaCl solution, collecting eluate, concentrating, and freeze drying to obtain product A mainly containing Fuscoporia obliqua polysaccharide;
s5, concentrating the supernatant collected in the step S2 under reduced pressure, slowly adding the concentrated supernatant into a macroporous resin chromatographic column by adopting a dynamic sample loading method, performing gradient elution by sequentially adopting deionized water and 30% ethanol solution by volume fraction, collecting ethanol eluent, concentrating under reduced pressure, and drying to obtain a product B mainly containing inonotus obliquus polyphenol; wherein, the sampling flow rate is preferably 1.5 times of the column volume/h, the elution is preferably carried out under the conditions of 40 ℃ and 0.06MPa during the gradient elution, and each gradient elution is 4 times of the column volume;
s6, mixing the product A and the product B to obtain the inonotus obliquus extract.
Example 3 Inonotus obliquus extract preparation (P3)
S1, taking the wild sporocarp of the inonotus obliquus, crushing into coarse powder, adding 85% ethanol solution according to the material-liquid ratio of 1:30m/v, carrying out reflux extraction at 85 ℃ for 3 times, 2 hours each time, carrying out reduced pressure filtration, and collecting extraction residues;
s2, taking the residues, adding deionized water into the residues according to the material-liquid ratio of 1:30m/v for reflux extraction, and performing reflux extraction at 100 ℃ for 3 times, 2 hours each time, so as to obtain a water extract containing the polysaccharide and the polyphenol of the inonotus obliquus; rotary evaporating the water extract to dryness, adding 95% ethanol solution at a material-to-liquid ratio of 1:5m/v, standing overnight, centrifuging, and collecting precipitate and supernatant;
s3, dissolving the collected precipitate in deionized water at room temperature; mixing the above polysaccharide solution and chloroform-n-butanol solution (mixed solution at volume ratio of 4: 1) at volume ratio of 4:1, shaking for 30min, and centrifuging; adding chloroform-n-butanol solution into water phase, repeating the above process for 3 times, and concentrating to obtain concentrated solution;
s4, adding 95% ethanol by volume fraction into the concentrated solution according to the proportion of 1:3v/v, precipitating overnight, centrifuging, collecting precipitate, washing the precipitate with absolute ethanol, acetone and petroleum ether in sequence, dissolving the washed precipitate in deionized water, and freeze-drying to obtain the inonotus obliquus crude polysaccharide; dissolving the obtained Fuscoporia obliqua polysaccharide in deionized water, centrifuging, collecting supernatant, ultrafiltering, and slowly adding into pretreated anion exchange column (DEAE-52) chromatographic column; eluting with 0.2M NaCl solution, collecting eluate, concentrating, and freeze drying to obtain product A mainly containing Fuscoporia obliqua polysaccharide;
s5, concentrating the supernatant collected in the step S2 under reduced pressure, slowly adding the concentrated supernatant into a macroporous resin chromatographic column by adopting a dynamic sample loading method, performing gradient elution by sequentially adopting deionized water and 60% ethanol solution by volume fraction, collecting ethanol eluent, concentrating under reduced pressure, and drying to obtain a product B mainly containing inonotus obliquus polyphenol; wherein, the sampling flow rate is preferably 3 times of the column volume/h, the elution is preferably carried out under the conditions of 45 ℃ and 0.03MPa during the gradient elution, and each gradient elution is 4 times of the column volume;
s6, mixing the product A and the product B to obtain the inonotus obliquus extract.
Comparative example 1 Inonotus obliquus extract (P4)
The difference compared to example 1 is that the preparation method of Inonotus obliquus extract is different (steroid compound is not removed), and the rest parameters are the same as example 1.
The preparation method of the inonotus obliquus extract comprises the following steps:
s1, taking the wild sporocarp of the inonotus obliquus, crushing into coarse powder, adding 80% ethanol solution according to the material-liquid ratio of 1:25m/v, carrying out reflux extraction at 85 ℃ for 3 times, 2 hours each time, carrying out reduced pressure filtration, and collecting filtrate and extraction residues; evaporating the collected filtrate by rotation, adding deionized water with the volume of 8 times of that of the filtrate for suspension, centrifuging, collecting precipitate, and drying to obtain a product a mainly containing the inonotus obliquus steroid compounds;
s2, taking the residues, adding deionized water into the residues according to the material-liquid ratio of 1:22m/v for reflux extraction, and performing reflux extraction at 90 ℃ for 3 times, 2 hours each time, so as to obtain a water extract containing the polysaccharide and the polyphenol of the inonotus obliquus; rotary evaporating the water extract to dryness, adding 90% ethanol solution according to the material-liquid ratio of 1:3m/v, standing overnight, centrifuging, and collecting precipitate and supernatant;
s3, dissolving the collected precipitate in deionized water at room temperature; mixing the above solution and chloroform-n-butanol solution (mixed solution at volume ratio of 4: 1) at volume ratio of 4:1, shaking for 30min, and centrifuging; adding chloroform-n-butanol solution into water phase, repeating the above process for 3 times, and concentrating to obtain concentrated solution;
s4, adding 95% ethanol by volume fraction into the concentrated solution according to the proportion of 1:3v/v, precipitating overnight, centrifuging, collecting precipitate, washing the precipitate with absolute ethanol, acetone and petroleum ether in sequence, dissolving the washed precipitate in deionized water, and freeze-drying to obtain the inonotus obliquus crude polysaccharide; dissolving the obtained Fuscoporia obliqua polysaccharide in deionized water, centrifuging, collecting supernatant, ultrafiltering, and slowly adding into pretreated anion exchange column (DEAE-52) chromatographic column; eluting with 0.2M NaCl solution, collecting eluate, concentrating, and freeze drying to obtain product A mainly containing Fuscoporia obliqua polysaccharide;
s5, concentrating the supernatant collected in the step S2 under reduced pressure, slowly adding the concentrated supernatant into a macroporous resin chromatographic column by adopting a dynamic sample loading method, performing gradient elution by sequentially adopting deionized water and 50% volume fraction ethanol solution, collecting ethanol eluent, concentrating under reduced pressure, and drying to obtain a product B mainly containing inonotus obliquus polyphenol; wherein, the sampling flow rate is preferably 2.5 times of the column volume/h, the elution is preferably carried out under the conditions of 42 ℃ and 0.05MPa during the gradient elution, and each gradient elution is 4 times of the column volume;
s6, mixing the product a, the product A and the product B to obtain the inonotus obliquus extract.
Comparative example 2 Inonotus obliquus extract (P5)
Compared with example 1, the difference is that the preparation method of the inonotus obliquus extract omits the steps of S5 and S6, and the obtained inonotus obliquus extract is the product A mainly containing inonotus obliquus polysaccharide, and the rest parameters are the same as example 1.
Comparative example 3 Inonotus obliquus extract (P6)
Compared with example 1, the difference is that the preparation method of the inonotus obliquus extract omits the steps S3 and S4, namely the obtained inonotus obliquus extract is the product B mainly containing inonotus obliquus polyphenol, and the rest parameters are the same as those of example 1.
Application example, preparation of capsule with weight-losing effect containing composition of the invention
Formula 1: (in 1000 pieces)
| Composition (I) | Prescription amount (g) |
| Orlistat | 60 |
| Inonotus obliquus extract (example 1) | 7.5 |
| Microcrystalline cellulose | 75 |
| Sodium carboxymethyl starch | 7.5 |
| Pregelatinized starch | 6 |
| HPMC | 3 |
| Colloidal silicon dioxide | 1 |
And (2) formula: (in 1000 pieces)
| Composition (I) | Prescription amount (g) |
| Orlistat | 60 |
| Inonotus obliquus extract (example 2) | 10 |
| Microcrystalline cellulose | 50 |
| Sodium carboxymethyl starch | 12 |
| Pregelatinized starch | 8 |
| HPMC | 2 |
| Colloidal silicon dioxide | 2 |
And (3) formula: (in 1000 pieces)
The preparation method comprises the following steps:
(1) crushing the materials, and sieving the crushed materials with a 65-mesh sieve;
(2) HPMC is weighed according to the prescription amount to prepare an aqueous solution with the mass concentration of 5 percent;
(3) weighing orlistat, inonotus obliquus extract, sodium carboxymethyl starch and pregelatinized starch according to the prescription amount, performing wet granulation on the materials in a wet granulator by using the prepared HPMC solution, and drying;
(4) adding microcrystalline cellulose and colloidal silicon dioxide into the dried material, mixing uniformly, grading, and subpackaging into gelatin empty capsules according to the dosage of each dose to obtain the final product.
Test example I study on the weight-reducing action of the composition of the present invention
1. Test materials
Male clean grade SD rats 90 (initial body weight 75-85g, housed in cages, free access to food and water for 7 days), high fat diet from commercial sources (high fat diet comprising 75% basal diet, 2% cholesterol, 0.5% sodium cholate, 15% lard, and 7.5% egg yolk).
2. Test method
2.1 Molding, grouping and administration
The test animals were randomly divided into 9 groups of 10 animals (no significant difference in body weight before treatment of rats in each group) by the obesity prevention model method, and each group and administration were as shown in table 1 below. Animals of each group were fed at 9 am, basal diet of the control group, high-fat diet of the model group and the test group, and diet taken at 7 pm, and dosed daily (the amount of diet was adjusted daily based on the fact that most animals had eaten up). The test groups were administered with the corresponding drugs (orlistat, inonotus obliquus extracts (P1-P3) at a dose of 10ml/kg twice at 9 am and 3 pm, and 0.5% sodium carboxymethylcellulose solution was used to prepare 3g/L, 0.375g/L, 0.5g/L, and 0.4g/L solutions, respectively, for the comparative examples 1-3 inonotus obliquus extracts (P4-P6) were used to prepare 0.375g/L solutions, respectively), and the blank control group and the model group were perfused with 0.5% CMC-Na solution of the same volume for 7 weeks.
TABLE 1 dosage and grouping
2.2 Observation index
2.2.1 weighing the animals of each group for 1 time per week, and calculating the weight gain; the results are shown in table 2 below.
2.2.2 oil distribution in Hair after application, the oil distribution in the hair of each group of animals (oil adhered to the hair, and visible to the naked eye) was observed every day, and the number of animals with oil distribution in hair was counted weekly, and the results are shown in Table 3 below.
2.2.3 fat index the total fat around the kidney and around the testis was dissected and weighed, and the fat index (fat index ═ fat/body weight) was calculated, the results of which are shown in table 4 below.
3 results
3.1 Effect on rat body weight
Table 2 weight change of rats before and after the test (χ ± s, n ═ 10)
Note: compared with the blank control group, the composition of the composition,*P＜0.05，**p is less than 0.01; in comparison to the set of models,#P＜0.05，##p is less than 0.01; compared with the orlistat group,1)P＜0.05，2)P＜0.01。
as can be seen from the table above, the difference between the initial body weight groups of the animal experiments of each group is not statistically significant, compared with the blank control group, the body weight gain of the model group is obviously greater than that of the blank control group after 7 weeks of the experiment, and the difference is very significant (P is less than 0.01), which shows that the model building of the obese rat model is successful. The weight gain of the orlistat group is obviously lower than that of the model group, and very significant difference exists (P is less than 0.01), so that the orlistat can be singly administered to effectively inhibit the weight gain of obese rats; compared with the orlistat group, the experimental groups 1-3 have very obvious difference, the weight gain of the rat after 7 weeks of administration is obviously lower than that of the orlistat group which is administered alone, and the results show that the simultaneous administration of the orlistat and the inonotus obliquus extract can more effectively inhibit the weight gain of the rat, and the orlistat and the inonotus obliquus extract have synergistic effect.
Surprisingly, the test group 4 showed a lower effect in inhibiting weight gain in rats than the orlistat group alone, consistent with the above "the presence of steroids in the Inonotus obliquus extract sacrifices a part of the orlistat weight loss effect"; the test groups 5 and 6 added with the Inonotus obliquus extracts obtained by different preparation methods have certain difference in weight reduction effect compared with the test example 1 group, but still better than the orlistat group which is singly added.
3.2 Effect on oil distribution to animal Hair
TABLE 3 statistics of the distribution of oil and fat in the hair of rats in each group
As can be seen from the results in table 3, after 1 week of orlistat alone, a part of the rats showed oil distribution in hair, and the number of rats showing oil distribution in hair gradually increased as the test proceeded; and the adverse gastrointestinal reaction of rats can be obviously improved by simultaneously administering the inonotus obliquus extracts P1-P6 and orlistat, the number of rats with hair fat distribution is obviously reduced, and particularly, the adverse gastrointestinal reaction of rats is not found by simultaneously administering the inonotus obliquus extracts P1-P3 and orlistat. The inonotus obliquus extract can improve or reduce gastrointestinal adverse reactions caused by orlistat to a certain extent, and the inonotus obliquus extract has the sequence of P1 & gt P6 & gt P5 & gt P4 according to the improvement effect.
3.3 Effect on fat index
TABLE 4 change in fat index of rats in each group
Note: compared with the blank control group, the composition of the composition,*P＜0.05，**p is less than 0.01; in comparison to the set of models,#P＜0.05，##p is less than 0.01; compared with the orlistat group,1)P＜0.05，2)P＜0.01。
as can be seen from the above table, the fat index of the model group is significantly increased (P < 0.01) compared with that of the blank control group; the fat index of the orlistat group and the rats in the test 1-6 groups is obviously reduced compared with that of the model group (P is less than 0.01); the fat index of rats 1-3 in the test group is significantly different (P is less than 0.05) compared with that of orlistat group, and the combination of the inonotus obliquus extract and orlistat can significantly reduce fat accumulation in rats, inhibit fat absorption and have excellent weight-reducing effect; the fat-reducing effect of the test group 4 was slightly inferior to that of the orlistat group, showing that the presence of the steroid compound had an adverse effect on the improvement of the weight-reducing effect.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A composition with weight-losing effect is characterized by at least comprising orlistat and inonotus obliquus extracts.
2. The composition according to claim 1, wherein the mass ratio of the inonotus obliquus extract to orlistat in the composition is 6.2:1-12:1, preferably 8:1-12: 1.
3. The composition according to claim 2, wherein the mass ratio of the Inonotus obliquus extract to orlistat in the composition is 6.2:1, preferably 7:1, more preferably 7.5:1, particularly 8:1, more particularly 8.5: 1.
4. The composition according to any one of claims 1 to 3, wherein the Inonotus obliquus extract contains no or little inonotus obliquus steroids.
5. The composition of claim 4, wherein the inonotus obliquus steroids include lanosterol, inonotus obliquus alcohol, and ergosterol.
6. The composition of claim 5, wherein the Inonotus obliquus extract consists essentially of Inonotus obliquus polysaccharides and Inonotus obliquus polyphenols.
7. The composition according to claim 1 or 2, wherein the inonotus obliquus extract is prepared by a method comprising the steps of:
s1, taking the wild sporocarp of the inonotus obliquus, crushing into coarse powder, adding 70-85% of ethanol solution by volume fraction into the coarse powder, performing reflux extraction at the temperature of 80-90 ℃ for 1-3 times, performing 1-3 hours each time, performing reduced pressure filtration, and collecting extraction residues;
s2, adding deionized water into the residue for reflux extraction to obtain a water extract containing the polysaccharide and the polyphenol of the inonotus obliquus; rotary evaporating the water extract to dryness, adding an ethanol solution with the volume fraction of 85-95%, standing overnight, centrifuging, and collecting a precipitate and a supernatant;
s3, removing proteins from the collected precipitate by adopting a Sevag method, then adding ethanol with the volume fraction of 85-95% again, precipitating overnight, centrifuging, collecting the precipitate, washing the precipitate by adopting absolute ethyl alcohol, acetone and petroleum ether in sequence, dissolving the washed precipitate in deionized water, and freeze-drying to obtain a product A;
s4, concentrating the supernatant collected in the step S2 under reduced pressure, slowly adding the concentrated supernatant into a macroporous resin chromatographic column, performing gradient elution by sequentially adopting deionized water and 30-60% volume fraction ethanol solution, collecting ethanol eluate, concentrating under reduced pressure, and drying to obtain a product B;
s5, mixing the product A and the product B to obtain the inonotus obliquus extract.
8. The composition as claimed in claim 7, wherein the step S3 further comprises the step of separating and purifying the product A.
9. The composition as claimed in claim 7, wherein in the step S2, the reflux extraction conditions with deionized water are as follows: the material-liquid ratio is 1: 20-30 m/v, the extraction temperature is 90-100 ℃, and the reflux extraction is carried out for 1-3 times, 1-2 h each time.
10. Use of a composition according to any one of claims 1 to 9 in the manufacture of a medicament for the prophylactic or therapeutic treatment of obesity and/or lipid lowering.
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| US20020016307A1 (en) * | 1999-10-27 | 2002-02-07 | Mullins John Jason Gentry | Pharmaceutical composition with both a lipase inhibitor and a lipophilic polysaccharide and an improved method for treating adiposity |
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