CN108542903A - A kind of pharmaceutical composition containing orlistat Yu plant origin lipase inhibitor - Google Patents
A kind of pharmaceutical composition containing orlistat Yu plant origin lipase inhibitor Download PDFInfo
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- CN108542903A CN108542903A CN201810322326.4A CN201810322326A CN108542903A CN 108542903 A CN108542903 A CN 108542903A CN 201810322326 A CN201810322326 A CN 201810322326A CN 108542903 A CN108542903 A CN 108542903A
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- orlistat
- lipase inhibitor
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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
- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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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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Abstract
The present invention relates to pharmaceutical technology field, more particularly to a kind of pharmaceutical composition containing orlistat Yu plant origin lipase inhibitor.The plant origin lipase inhibitor is the Polyphenols lipase inhibitor extracted from tealeaves.In vitro test is the results show that the orlistat with Polyphenols lipase inhibitor is 1 in molar ratio:10~10:Inhibit the interaction index of lipase active to be below 1 when 1 range, the two is prompted to produce the fatty enzyme inhibition of collaboration.Animal test results show that the composition containing orlistat and Polyphenols lipase inhibitor is administered alone group better than orlistat group to the body weight control effect of nutritive obesity in rats with Polyphenols lipase inhibitor, further demonstrates the generation of synergistic effect.In addition, the Polyphenols lipase inhibitor can reduce orlistat gastrointestinal side-effect beastly, alleviate the adverse reactions such as just of oil mark, fats/oils.
Description
Technical field
The present invention relates to pharmaceutical technology fields, more particularly to a kind of to contain orlistat and plant origin lipase inhibitor
Pharmaceutical composition.
Background technology
Orlistat (orlistat) is to research and develop lipase inhibitor class slimming drugs, trade name by company of Roche Group
Xenical, the last century nineties end take the lead in listing in America and Europe, are eaten by China in Discussion on Chinese Listed, and in 2005 within 2001
The approval of product Drug Administration switchs to non-prescribed medicine.Its entitled N- formyls-L-Leu (s) -1 of chemistry [(2s, 3s) 3- oneself
- 4 oxygroup -2- glycidyl methyl of base] ten diester, also referred to as tetrahydrolipostatin (Tetrahydrolipstatin, THL) they are a kind of
Semi-synthetic lipstatin derivative, chemical structural formula are shown below：
The serine residue of orlistat and stomach pancreatic lipase forms covalence key, can not will be in food to make enzyme inactivate
Triglyceride hydrolysis at absorbable aliphatic acid, and then reduce the uptake of fat.Currently, orlistat is unique both at home and abroad
A kind of chemical slimming drugs for not influencing appetite, not acting on central nervous system, security features are superior, Bray GA in《Willow leaf
Knife》Orlistat is described as " most safe " in the article for the entitled Management of Obesity that magazine is delivered
(safest) slimming drugs.However, can only inhibit 30% fat absorption after orlistat is oral, Bray GA et al. are in delivering
《Lancet》The article of an entitled Management of Obesity fat-reducing effect of orlistat is assessed as
" modest (medium) ", not as good as the appetite inhibitor class slimming drugs listed in the recent period.In view of the superior safety of orlistat, having must
The weight loss effect that orlistat preparation is improved by the means of drug or pharmacy, to expand its clinical application, so as to answering
To increasingly severe obesity morbidity situation.
The lipase inhibitor for being approved listing both at home and abroad only has orlistat with west for Li Sita (cetilistat)
Two kinds, the former can by it is fully synthetic or it is semi-synthetic obtain, the latter is only capable of being prepared by fully synthetic.In addition to synthetic,
Also contain abundant lipase inhibitor in plant, structure type includes Polyphenols, saponins, terpene, flavonoids, biology
Bases etc..It is all that the lipase inhibitor extracted in tealeaves not only has that derive from a wealth of sources, various structures, specificity is high, toxicity is low etc.
More advantages, but also may generate the loss of weight cooperateed with orlistat because the different active site of lipase is acted on and make
With.
Nakai M et al. (Journal of Agricultural and Food Chemistry, 2005,53 (11):
4593~4598) lipase inhibiting activity of the 54 kinds of polyphenol compounds extracted in tealeaves is determined, is as a result sent out
Existing related compound inhibits IC when lipase500.048~>Between 20 μM, it is less than Li Qiang et al. on the whole in its summary
Described other plant source lipase inhibitor (research and development of natural products .2015,27:360~366), however
Introduction temporarily without the lipase inhibitor and the specific binding site of lipase that are extracted in tealeaves in the prior art, also without orlistat
Whether the introduction of synergistic effect is generated after combining with the lipase inhibitor extracted in tealeaves.
Invention content
The technical issues of in order to overcome in the presence of the prior art, the purpose of the present invention is to provide one kind containing Ao Lisi
He with tealeaves in the pharmaceutical composition of Polyphenols lipase inhibitor extracted, the active constituent in the pharmaceutical composition can generate
The fatty enzyme inhibition of collaboration, and there is good loss of weight effect, it can be used for treating and preventing obesity.
Above-mentioned purpose that the invention is realized by the following technical scheme：
The present invention provides a kind of pharmaceutical composition for treating and preventing obesity, which includes Ao Li
He and plant origin lipase inhibitor are taken charge of, specifically, the plant origin lipase inhibitor is extracted from tealeaves
Polyphenols lipase inhibitor.
Specifically, the lipase inhibitor extracted in the tealeaves is in the compound that structural formula is shown below
It is at least one.
In vitro test is the results show that provided by the present invention for Ao Lisi in the pharmaceutical composition for the treatment of and prevention obesity
He with tealeaves in the Polyphenols lipase inhibitor that extracts in molar ratio (ratio of the amount of substance) be 1:10~10:1 range
When inhibit the interaction index of lipase active to be below 1, both prompt the fatty enzyme inhibition for producing collaboration.
Preferably, when Polyphenols lipase inhibitor be I compound represented of formula (compound 1), the compound 1 with
The molar ratio of orlistat is 1:9~1:6.It is highly preferred that the compound 1 and the molar ratio of orlistat are 1:7.75.
Preferably, when Polyphenols lipase inhibitor is II compound represented of formula (compound 2), the compound 2
Molar ratio with orlistat is 1:4~1:2.It is highly preferred that the compound 2 and the molar ratio of orlistat are 1:3.
Preferably, when Polyphenols lipase inhibitor is III compound represented of formula (compound 3), the compound 3
Molar ratio with orlistat is 1:2~2:1.It is highly preferred that the compound 3 and the molar ratio of orlistat are 1.25:
1。
Preferably, when Polyphenols lipase inhibitor is VI compound represented of formula (compound 4), the compound 4
Molar ratio with orlistat is 1:4~1:1.It is highly preferred that the compound 4 and the molar ratio of orlistat are 1:2.5.
On the other hand, animal test results are shown, provided by the present invention for treating and preventing the pharmaceutical composition of obesity
The Polyphenols lipase inhibitor extracted in orlistat and tealeaves in object is by the most preferred molar ratio measured by vitro test
Combination, it is identical in accumulated dose for calculation in the molar ratio, and the dosage of orlistat and Polyphenols lipase inhibitor is equal in composition
Under the premise of being administered alone group less than the two, composition is better than orlistat group to the body weight control effect of nutritive obesity in rats
It is administered alone group with Polyphenols lipase inhibitor, further demonstrates the generation of synergistic effect.
At the same time, it inventor have further surprisingly found that, when orlistat is shared with Polyphenols lipase inhibitor, tests
The size of animal that grease distribution occurs in Hair of Rats in group substantially reduces, and prompts pharmaceutical composition provided by the invention that can reduce
There is the probability of grease in Hair of Rats, and the Polyphenols lipase inhibitor can reduce orlistat stomach and intestine beastly
The adverse reactions such as just of oil mark, fats/oils are alleviated in side effect.
Pharmaceutical composition provided by the present invention for treating and preventing obesity can be used directly, can also add one
Kind or a variety of pharmaceutical excipients oral preparation is simultaneously made using formulation method well-known to those skilled in the art, as powder,
Granula, capsule, tablet, pill etc..The formulation method well known to those skilled in the art can refer to but be not limited to Cui Fu
Moral is edited,《Pharmacy》(the 7th edition) (People's Health Publisher's publication), is incorporated herein by reference.It specifically, can will be difficult to understand
The Polyphenols lipase inhibitor extracted in Li Sita, the tealeaves is mutually mixed at least one pharmaceutically acceptable excipient
It closes, the excipient such as citric acid or Dicalcium Phosphate, or：(a) filler or incremental agent, for example, starch, lactose, sucrose,
Glucose, mannitol and silicic acid；(b) adhesive, for example, cellulose derivative, starch, alginate, gelatin, polyvinyl pyrrole
Pyrrolidone, sucrose and acacia gum；(c) disintegrant, for example, agar, calcium carbonate, potato or tapioca, alginic acid, friendship
Join carmethose, composition silicate and sodium carbonate；(d) solution retardant, for example, paraffin；(e) sorbefacient, such as
Quaternary ammonium compound；(f) wetting agent, for example, cetanol and glycerin monostearate, magnesium stearate etc.；(g) adsorbent, for example, it is high
Ridge soil and soap clay；(h) lubricant, for example, talcum powder, calcium stearate, magnesium stearate, solid polyglycols, lauryl sulfate
Sodium or their mixture.
Preferably, pharmaceutical composition provided by the invention adds suitable pharmaceutic adjuvant and capsule is made.
Compared with prior art, advantage of the invention is that：
The present invention discloses the Polyphenols lipase inhibitor extracted in orlistat and tealeaves (shown in I-formula of formula VI for the first time
Compound) composition have collaboration fatty enzyme inhibition, be applied to treat or prevent obesity have it is good
Cooperative gain effect is significantly better than orlistat group to the body weight control effect of nutritive obesity in rats and presses down with polyphenol quasi-lipase
Preparation is administered alone group, meanwhile, it is surprising that can also to reduce orlistat unpleasant for Polyphenols lipase inhibitor
Gastrointestinal side-effect, alleviate the adverse reactions such as just of oil mark, fats/oils, achieve unexpected effect.
Description of the drawings
Fig. 1 be interaction index (Y) when compound 1 is combined with orlistat and both the relational graph of molar ratio (rub
You are than range 1:10~10:1).
Fig. 2 be interaction index (Y) when compound 1 is combined with orlistat and both molar ratio relational graph it is (excellent
Select molar ratio range).
Fig. 3 be interaction index (Y) when compound 2 is combined with orlistat and both the relational graph of molar ratio (rub
You are than range 1:10~10:1).
Fig. 4 be interaction index (Y) when compound 2 is combined with orlistat and both molar ratio relational graph it is (excellent
Select molar ratio range).
Fig. 5 be interaction index (Y) when compound 3 is combined with orlistat and both the relational graph of molar ratio (rub
You are than range 1:10~10:1).
Fig. 6 be the relational graph of both interaction indexes (Y) when compound 3 is combined with orlistat molar ratio (preferably
Molar ratio range).
Fig. 7 be both interaction indexes (Y) when compound 4 is combined with orlistat molar ratio relational graph (mole
Than range 1:10~10:1).
Fig. 8 be the relational graph of both interaction indexes (Y) when compound 4 is combined with orlistat molar ratio (preferably
Molar ratio range).
Specific implementation mode
The present invention is made with specific embodiment with reference to the accompanying drawings of the specification and further being elaborated, the embodiment
It is served only for explaining the present invention, be not intended to limit the scope of the present invention.Test method used in following embodiments is such as without spy
Different explanation, is conventional method；Used material, reagent etc., unless otherwise specified, for the reagent commercially obtained
And material.
First, the applicant entrusts Zhong Shanwanyuan new drug developments Co., Ltd (hereinafter referred " middle mountain ten thousand is remote ") to synthesize this
Polyphenols lipase inhibitor described in invention pharmaceutical composition, the quality report far provided according to middle mountain ten thousand show, institute
The purity of the compound 1-4 stated is 99.7% or more.
Secondly, the present invention is using Nakai M et al. (Journal of Agricultural and Food
Chemistry,2005, 53(11):4593~4598) the lipase inhibiting activity assay method disclosed by, and with interaction
Index (Y) is index, has investigated orlistat with single Polyphenols lipase inhibitor with 1:10~10:1 mol ratio combination
Afterwards to the coordinate repression of lipase active, and best molar ratio is screened, as a result seen shown in attached drawing 1-8.Wherein, mutually
The computational methods of action index (Y) are shown below.
IC in above formula50(A)With IC50(B)When indicating that orlistat is individually handled with one kind in corresponding compound 1-4 respectively
To the IC of lipase50Value, IC50(mixA)With IC50(mixB)Indicate that mixed system generates Ao Lisi when half inhibits to lipase respectively
The concentration of he and corresponding Polyphenols lipase inhibitor.
By attached drawing 1,3,5,7 it is found that orlistat is combined with compound 1-4 respectively, 1:10~10:1 molar ratio model
It encloses the interior interaction index (Y) for inhibiting lipase active and is below 1, there is the fatty enzyme inhibition of collaboration.And when change
It closes object 1 to combine with orlistat, 1:9~1:Inhibit the better of lipase active in 6 molar ratio range；Work as compound
2 combine with orlistat, 1:4~1:Inhibit the better of lipase active in 2 molar ratio range；When compound 3 with
Orlistat combines, 1:2~2:Inhibit the better of lipase active in 1 molar ratio range；When compound 4 and Austria's profit
It takes charge of him to combine, 1:4~1:Inhibit the better of lipase active in 1 molar ratio range.
By attached drawing 2 it is found that when compound 1 is combined with orlistat, 1:7.75 molar ratio inhibits lipase active
Best results.
By attached drawing 4 it is found that when compound 2 is combined with orlistat, 1:3 molar ratio inhibits the effect of lipase active
Most preferably.
By attached drawing 6 it is found that when compound 3 is combined with orlistat, 1.25:1 molar ratio inhibits lipase active
Best results.
By attached drawing 8 it is found that when compound 4 is combined with orlistat, 1:2.5 molar ratio inhibits the effect of lipase active
Fruit is best.
Antiobesity action of the combination of test example one, orlistat and Polyphenols lipase inhibitor to nutritive obesity in rats
This item test method is delivered using Liu Jingru et al.《Antiobesity action of the orlistat to nutritive obesity in rats》
(Chinese experimental pharmacology of traditional Chinese medical formulae magazine, 2013,19 (07):Following administration group is arranged in method disclosed by 186-188.)：
1) blank control group；
2) model group；
3) orlistat group；
4) test group A1-4；
5) experiment group B1-4,
6) test group C,
7) test group D, every group of 15 rats.
Wherein, the definition of blank control group, model group and orlistat group and the disclosures such as processing method and Liu Jingru is interior
Hold consistent；Test group A1-4While feeding rat with nutritional feed, compound 1-4 gavages are respectively adopted, it is pre- before gavage
Processing method is with orlistat group, and dosage is identical as orlistat group by the gauge of substance, i.e. 0.121mmol/kg/d.Test group
B1-4While feeding rat with nutritional feed, by compound 1-4 with orlistat according to optimal measured by vitro test
The amount of the substance of choosing compares gavage after combination, and the preprocess method before gavage is with orlistat group, two kinds of active components in combination
Accumulated dose is identical as orlistat group by the gauge of substance, i.e. 0.121mmol/kg/d.Test group C is fed with nutritional feed
While rat, filled using Epigallo-catechin gallate (EGCG) (EGCG is purchased from Shaanxi Sen Fu natural products Co., Ltd)
Stomach, the preprocess method before gavage is with orlistat group, and dosage is identical as orlistat group by the gauge of substance, i.e.,
0.121mmol/kg/d.Test group D with nutritional feed while feeding rat, using epigallocatechin gallic acid
Ester presses 1 with orlistat:The amount of 1 substance compares gavage after combination, and the preprocess method before gavage is with orlistat group, two in combination
The accumulated dose of kind active constituent is identical as orlistat group by the gauge of substance, i.e. 0.121mmol/kg/d.Successive administration 7 weeks
Afterwards, the changes of weight of each group animal is observed, and counts the size of animal that grease distribution occurs in nutritive obesity in rats hair, is calculated
The probability for grease occur, as a result as shown in the following table 1 and 2.
1 each rats in test groups of table be administered 7 weeks after changes of weight result
| Group | Feed and drug | Weightening, mean value ± SD (g) |
| Blank control group | Normal diet | 178.97±36.30 |
| Model group | Nutritional feed | 225.83±37.75a |
| Orlistat group | Nutritional feed+orlistat | 186.11±30.00b |
| Test group A1 | Nutritional feed+compound 1 | 176.02±29.05b* |
| Test group A2 | Nutritional feed+compound 2 | 178.34±30.10b* |
| Test group A3 | Nutritional feed+compound 3 | 172.58±28.42b* |
| Test group A4 | Nutritional feed+compound 4 | 175.75±29.60b* |
| Experiment group B1 | 1/ orlistat of nutritional feed+compound combination (1:7.75) | 109.24±20.00b,c,d |
| Experiment group B2 | 2/ orlistat of nutritional feed+compound combination (1:3) | 107.57±23.70b,c,d |
| Experiment group B3 | 3/ orlistat of nutritional feed+compound combination (1.25:1) | 102.30±21.05b,c,d |
| Experiment group B4 | 4/ orlistat of nutritional feed+compound combination (1:2.5) | 105.00±22.62b,c,d |
| Test C | Nutritional feed+EGCG | 177.26±43.05b* |
| Test D | Nutritional feed+EGCG/ orlistats combination (1:1) | 172.95±41.04b* |
Note：aP compared with blank control group<0.01, t examines
bThe P compared with model group<0.01, t examines
b*Compared with model group, P<0.01, but compared with orlistat group, P>0.05, equal t is examined
cWith orlistat group ratio P<0.01, t examines
dThe P compared with corresponding A group<0.01, t examines
The results show that when compound 1~4 is individually administered, the inhibition of auxotype obese rat weight gain is made
With suitable with orlistat, but and accumulated dose (according to the gauge of substance) and it is administered alone with orlistat administering drug combinations respectively
When orlistat is suitable, administering drug combinations are significantly better than what orlistat was administered alone to the increase of auxotype obese rat weight
Effect (P<0.01), to which the loss of weight that explanation produces collaboration acts on.In addition, the invention demonstrates that, EGCG is combined with orlistat
Using the increased effect of inhibition rat body weight is slightly better than individually giving EGCG groups or individually gives orlistat group, but without showing
Sex differernce is write, shows that EGCG combines the effect for not generating collaboration with orlistat.The above result shows that only and when specific
Polyphenols lipase inhibitor and orlistat combination application, could obtain the fat-reducing effect of collaboration.
2 each rats in test groups of table be administered 7 weeks after changes of weight result
The results show that after individually giving orlistat 1 week, size of animal that grease distribution occurs in Hair of Rats is 9,7
Zhou Houwei 15, and compound 1-4 and orlistat combination are given simultaneously, Hair of Rats can be substantially reduced and grease distribution occur
Size of animal, there is hair oil spilling phenomenon in only 2 rats after administration 7 weeks, show that the compounds of this invention 1-4 is closed with orlistat
Hair of Rats is caused the probability of grease occur with orlistat can be reduced, the compound 1-4, which can reduce orlistat, to make us not
Pleasant gastrointestinal side-effect alleviates the adverse reactions such as just of oil mark, fats/oils.In addition, the invention demonstrates that, EGCG and orlistat
Combination does not significantly reduce Hair of Rats and the probability of grease occurs, the above result shows that, only and when specific Polyphenols fat
Enzyme inhibitor and orlistat combination application could obtain the effect of the inhibition hair oil spilling phenomenon of collaboration.
It is prepared by 1 capsule of embodiment
Preparation of the embodiment 1 containing orlistat Yu the capsule of compound 1
Prescription：(pressing 1000 granulas)
Preparation process：
Respectively by lauryl sodium sulfate, crospovidone, carboxyrnethyl starch sodium, microcrystalline cellulose, orlistat, compound
1 powder crosses 80 mesh sieve, spare.Weigh the lauryl sodium sulfate of recipe quantity, crospovidone, carboxyrnethyl starch sodium, microcrystalline cellulose
Lauryl sodium sulfate, crospovidone, carboxyrnethyl starch sodium, are first uniformly mixed by element, orlistat, 1 powder of compound, then add
Enter microcrystalline cellulose, orlistat, compound 1 to be uniformly mixed, crosses 80 mesh and sieve twice.Mixed powder is slowly added to contain 10%
50% ethanol solution of PVP K30, softwood processed, 20 mesh squeeze sieving pelleting, and wet granular sets 30 DEG C of air dry oven drying 6
Hour, it takes out 20 mesh sieves, is packed into No. 0 capsule to obtain the final product.
It is prepared by 2 tablet of embodiment
Preparation of the embodiment 1 containing orlistat Yu the tablet of compound 2
Prescription：
Preparation process：
Orlistat, compound 2 are weighed by recipe quantity, using microcrystalline cellulose as filler, croscarmellose sodium,
Polyvinylpyrrolidone is disintegrant, and 60% ethanol solutions of 5%PVP are binder, and superfine silica gel powder is glidant, uses fluid bed
One-step palletizing, then tabletting to get.
It is prepared by 3 granule of embodiment
Preparation of the embodiment 3 containing orlistat Yu the granule of compound 3
Prescription：
Preparation process：
Orlistat, compound 3, starch, dextrin, the cane sugar powder for weighing recipe quantity are uniformly mixed.Separately by suitable 80%
Ethyl alcohol is incorporated in mixed-powder, is uniformly mixed, softwood is made, and wet grain is made by 18 mesh nylon mesh, 60 DEG C or so dryings, and 20
Mesh sieve, packing to get.
It is prepared by 4 sustained release tablets of embodiment
Preparation of the embodiment 4 containing orlistat Yu the sustained release tablets of compound 4
Prescription：
Preparation process：It is prepared into sustained release tablets by the preparation process of sustained release tablets.
It the above is only the preferred embodiment of the present invention, it is noted that above-mentioned preferred embodiment is not construed as pair
The limitation of the present invention, protection scope of the present invention should be subject to claim limited range.For the art
For those of ordinary skill, without departing from the spirit and scope of the present invention, several improvements and modifications can also be made, these change
Protection scope of the present invention is also should be regarded as into retouching.
Claims (10)
1. a kind of pharmaceutical composition for treating and preventing obesity, which is characterized in that include that orlistat comes with plant
The molar ratio of source lipase inhibitor, the orlistat and plant origin lipase inhibitor is 1:10~10:1.
2. pharmaceutical composition according to claim 1, which is characterized in that the plant origin lipase inhibitor is selected from
At least one of structural formula such as formula I, formula II, formula III, VI compound represented of formula；
3. pharmaceutical composition according to claim 2, which is characterized in that the plant origin lipase inhibitor is selected from
The molar ratio of structural formula such as I compound represented of formula, I compound represented of formula and orlistat is 1:9~1:6.
4. pharmaceutical composition according to claim 3, which is characterized in that I compound represented of formula and Ao Lisi
His molar ratio is 1:7.75.
5. pharmaceutical composition according to claim 2, which is characterized in that the plant origin lipase inhibitor is selected from
The molar ratio of structural formula such as II compound represented of formula, II compound represented of formula and orlistat is 1:4~1:2.
6. pharmaceutical composition according to claim 5, which is characterized in that II compound represented of formula and Ao Lisi
His molar ratio is 1:3.
7. pharmaceutical composition according to claim 2, which is characterized in that the plant origin lipase inhibitor is selected from
The molar ratio of structural formula such as III compound represented of formula, III compound represented of formula and orlistat is 1:2~2:1.
8. pharmaceutical composition according to claim 7, which is characterized in that III compound represented of formula and Ao Lisi
His molar ratio is 1.25:1.
9. pharmaceutical composition according to claim 2, which is characterized in that the plant origin lipase inhibitor is selected from
The molar ratio of structural formula such as VI compound represented of formula, VI compound represented of formula and orlistat is 1:4~1:1.
10. pharmaceutical composition according to claim 9, which is characterized in that VI compound represented of formula and Austria's profit
It is 1 to take charge of his molar ratio:2.5.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810322326.4A CN108542903B (en) | 2018-04-11 | 2018-04-11 | A kind of pharmaceutical composition containing orlistat Yu plant origin lipase inhibitor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810322326.4A CN108542903B (en) | 2018-04-11 | 2018-04-11 | A kind of pharmaceutical composition containing orlistat Yu plant origin lipase inhibitor |
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| CN108542903B CN108542903B (en) | 2019-02-26 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112263575A (en) * | 2020-10-26 | 2021-01-26 | 中山万汉制药有限公司 | Composition containing orlistat and indoxyl acetamide compound and application thereof |
| WO2021097651A1 (en) * | 2019-11-19 | 2021-05-27 | 中山万汉制药有限公司 | Pharmaceutical composition comprising orlistat and plant-derived lipase inhibitor |
| CN114159480A (en) * | 2022-01-19 | 2022-03-11 | 广州臻卓生物技术有限公司 | Composition with weight-losing effect and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1980655A (en) * | 2004-07-05 | 2007-06-13 | 三得利株式会社 | Lipase inhibitor |
| CN1989123A (en) * | 2004-05-27 | 2007-06-27 | 三得利株式会社 | Epigallocatechin dimers or trimers having lipase inhibitory activity and/or antioxidative activity |
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2018
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| CN1989123A (en) * | 2004-05-27 | 2007-06-27 | 三得利株式会社 | Epigallocatechin dimers or trimers having lipase inhibitory activity and/or antioxidative activity |
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| MASAAKI NAKAI等: "Inhibitory Effects of Oolong Tea Polyphenols on Pancreatic Lipase in Vitro", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021097651A1 (en) * | 2019-11-19 | 2021-05-27 | 中山万汉制药有限公司 | Pharmaceutical composition comprising orlistat and plant-derived lipase inhibitor |
| CN112263575A (en) * | 2020-10-26 | 2021-01-26 | 中山万汉制药有限公司 | Composition containing orlistat and indoxyl acetamide compound and application thereof |
| CN114159480A (en) * | 2022-01-19 | 2022-03-11 | 广州臻卓生物技术有限公司 | Composition with weight-losing effect and preparation method and application thereof |
| CN114159480B (en) * | 2022-01-19 | 2022-08-30 | 夏文华 | Composition with weight-losing effect and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108542903B (en) | 2019-02-26 |
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