CN108524495B - Purposes of the orlistat in the drug of preparation treatment constipation - Google Patents
Purposes of the orlistat in the drug of preparation treatment constipation Download PDFInfo
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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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
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Abstract
The invention belongs to field of medicaments, and in particular to purposes of the orlistat in preparation treatment constipation drug.The drug includes a effective amount of orlistat and a effective amount of konjac mannan oligosaccharide with different molecular weight, drug of the present invention is made of konjac mannan oligosaccharide and orlistat by a certain amount ratio, it is surprised to find, the drug has the function of significantly improving constipation symptom, oil mark caused by taking orlistat, fatty stool adverse reaction can significantly be mitigated simultaneously, achieve significant progress compared with prior art.
Description
Technical field
The invention belongs to field of medicaments, and in particular to purposes of the Li Sita in the drug of preparation treatment constipation.
Background technique
Orlistat is a kind of unique non-nervous centralis slimming drugs, it is long-acting usually as a kind of novel slimming medicine
With potent specific gastrointestinal lipase inhibitor, pass through the activity with stomach and enteral gastrointestinal lipase and pancreatic lipase
Serine position combines and forms covalent bond, and lipase is made to lose activity, and prevents lipolysis, absorption and utilization in food, thus
Achieve the purpose that weight-reducing.
Although orlistat has significant effect in weight-reducing, there is also more ignorable bad anti-simultaneously
It answers, common adverse reaction includes that oiliness spot, defecation are promptly felt, the exhaust of oiliness spot, stomach and intestine increases, fatty stool, increases
Add defecation and faecal incontinence.Wherein, increase this adverse reaction of defecation and embody orlistat in treatment constipation with theory
On feasibility, but to belong to a complicated symptom comprehensive for constipation, further includes that excrement is dry and hard, defecation expense in addition to defecation is reduced
The symptoms such as power, defecation discomfort, it is clear that according to the knowledge grasped at present, orlistat is acted on without above-mentioned symptom is mitigated.
Meanwhile because above-mentioned adverse reaction caused by orlistat be it is simultaneous, represent with orlistat treat constipation when
It will appear the adverse reactions such as above-mentioned oiliness spot.Therefore, if being used to treat constipation for orlistat, problem to be solved is drop
It is low take oiliness spot, defecation caused by orlistat promptly feel, oiliness spot, stomach and intestine exhaust increase, fatty stool and
The adverse reactions such as faecal incontinence, while guaranteeing that it increases defecation, and not yet occur can achieve the skill of above-mentioned purpose at present
Art scheme.
Konjaku glucomannan (KGM) is a kind of water-soluble natural macromolecule amylose, has been widely used in environmental protection, food
Product, medicine, chemical industry and biological field.KGM is by β -1,4 pyranose glycosidic bond by β-D-MANNOSE by 1:1.6's or 1:1.69
Molar ratio is formed by connecting, with the presence of an acetyl group (Kato k, k matsuda.Studies on every 19 saccharide residues
the chemical structure of konjacmannan[J].Journal of Agriculture and
Biological Chemistry, 1969,33:1446-1453).Since natural KGM molecular weight is excessive, viscosity is excessively high, dissolution
Spend it is small so that its application is received and is greatly limited, currently, it is main made by chemical or bio-modification method it is natural
KGM degradation obtains different molecular weight and the konjac mannan oligosaccharide with different physico-chemical property and biological function
(KOGM), and the KOGM of different molecular weight in terms of materialization and biological function have significant difference.And by konjaku glucomannan
It is combined with orlistat as a kind of drug for treating constipation, is not yet disclosed at present.
Summary of the invention
The present invention is intended to provide purposes of the orlistat in preparation treatment constipation drug, with significant defaecation function
Can, and adverse reaction is few.
In order to achieve the above object, the invention adopts the following technical scheme: orlistat is in preparation treatment constipation drug
Purposes.
" constipation " described herein has following symptom: awareness of defecation is few, and bowel frequency is also few；Defecation is difficult, laborious；Defecation is unsmooth；
Dry and hard excrement, it is hard just, the not clean sense of defecation；Constipation is with abdominal pain or abdominal discomfort.
Preferably, the drug includes a effective amount of orlistat and a effective amount of Amorphophallus rivieri glucomannan with different molecular weight
Reveal oligosaccharide.When the drug is for that can separate and take or take simultaneously when treating constipation, day dosage is 120mg tid, usually
It is taken in about 1~2h after ingesting.
Preferably, it is 1.14 × 10 that the konjac mannan oligosaccharide with different molecular weight, which includes molecular weight,5u、
4.23×105U and 6.01 × 105The konjac mannan oligosaccharide of u.It is highly preferred that the molecular weight is 1.14 × 105The konjaku of u
Oligo-glucomannan accounting is 8~22wt%.
Preferably, the drug can significantly reduce adverse reaction caused by orlistat, and the adverse reaction refers to oiliness
Spot and fatty stool.
Another object of the present invention is to provide a kind of drug for treating constipation, the drug include a effective amount of orlistat and
A effective amount of konjac mannan oligosaccharide with different molecular weight.
Preferably, it is 1.14 × 10 that the konjac mannan oligosaccharide with different molecular weight, which includes molecular weight,5u、
4.23×105U and 6.01 × 105The konjac mannan oligosaccharide of u.
Preferably, the molecular weight is 1.14 × 105The konjac mannan oligosaccharide accounting of u is 8~22wt%.
Preferably, the preferred raw material proportioning of the drug are as follows:
The orlistat of 0.1~10% (w/w),
5~25% (w/w) have the konjac mannan oligosaccharide of different molecular weight, the konjaku with different molecular weight
Oligo-glucomannan includes that molecular weight is 1.14 × 105u、4.23×105U and 6.01 × 105The konjac mannan oligosaccharide of u,
With,
The pharmaceutically available auxiliary material of surplus.
Preferably, " pharmaceutically available auxiliary material " described herein selects conventional suitable auxiliary material according to the different of dosage form.Tool
Body, which can be made into the dosage form that tablet, capsule, coated tablet, disintegrating agent etc. pharmaceutically receive.Wherein tablet is this
Preferred dosage form is invented, tablet can be made of active constituent and auxiliary material, and the auxiliary material includes pharmaceutically common filler, bonding
Agent.
Preferably, the preferred raw material proportioning of the drug are as follows:
The orlistat of 0.1~10% (w/w),
5~25% (w/w) have the konjac mannan oligosaccharide of different molecular weight, the konjaku with different molecular weight
Oligo-glucomannan includes that molecular weight is 1.14 × 105u、4.23×105U and 6.01 × 105The konjac mannan oligosaccharide of u, and
Molecular weight is 1.14 × 105The konjac mannan oligosaccharide accounting of u be 8~22wt%, and, surplus it is pharmaceutically available auxiliary
Material.
Before the filing date, take defecation caused by orlistat promptly feel, oiliness spot, stomach and intestine exhaust increase, fat
Property stool, increase defecation and faecal incontinence typically as a kind of adverse reaction, be difficult to expect being used for treating constipation.Cause
For, although orlistat has the function of increasing defecation, it is not obvious, and mitigation effect is had no to the other symptoms of constipation,
And it is accompanied by other adverse reactions simultaneously, it is meant that, at least before the applying date, orlistat is not appropriate for as treatment constipation
Drug, it is often more important that if considering to reduce the adverse reaction of orlistat, then theoretically its effect also phase for increasing defecation
Therefore the decrease answered before the applying date, is still difficult to expect orlistat as a kind of drug for treating constipation.
And it is using the technical problem that orlistat is solved as constipation therapy drug needs: is reducing caused by orlistat
While other adverse reaction (such as oil mark, fatty are defecated), increases it and mitigation of constipation symptom is acted on.In other words, it needs
Effect to be achieved is after taking drug of the present invention, and the symptoms such as excrement amount is reduced, excrement is dry and hard, defecation is laborious, defecation is uncomfortable obtain
Mitigate to significant, and oil mark, defecation promptly feels, stomach and intestine exhaust increases, fatty is defecated and faecal incontinence at least one disease
Shape is significantly mitigated.Then, inventor gropes by long-term practice with test, it has unexpectedly been found that, konjac mannan is oligomeric
Sugar can significantly reduce take orlistat after the adverse reactions such as caused oil mark, fatty stool, but this is not inventor
It is desired, because although adverse reaction reduces, it increases defecation and also reduces, and to other diseases of constipation
Shape is acted on without mitigation.It is meant that the composition of konjac mannan oligosaccharide and orlistat has no the effect for the treatment of constipation.
On this basis, inventor gropes by countless tests, it is found that the konjac mannan that different molecular weight is added is low
Glycan is larger to the difference between the effects of orlistat, and when in corresponding ratio three kinds of different molecular weights (1.14 × 10 of addition5u、
4.23×105U and 6.01 × 105When konjac mannan oligosaccharide u), acted on orlistat, because orlistat draws after taking
Oil mark and fatty the stool adverse reaction risen significantly mitigates, and patient's defecation frequency increases, defecation condition and fecal character
Be improved significantly, but disappointed is still to have some patientss reflection with abdominal pain or abdominal discomfort.And in order to further
Optimize drug, inventor is it was unexpectedly observed that make its middle-molecular-weihydroxyethyl 1.14 × 105The konjac mannan oligosaccharide accounting of u be 8~
22wt% can mitigate the abdominal pain or abdominal discomfort phenomenon of constipation patient significantly.That is, when three kinds of different moleculars are added
When the konjac mannan oligosaccharide of amount, and make its middle-molecular-weihydroxyethyl 1.14 × 105The konjac mannan oligosaccharide accounting of u is 8
On the one hand~22wt% can significantly reduce caused oil mark, fatty stool adverse reaction after orlistat, on the other hand,
It has significant treatment effect to constipation, and for obtaining the principle mechanisms of said effect, inventor is not yet clear.
The invention has the following advantages that
Drug of the present invention is made of konjac mannan oligosaccharide and orlistat by a certain amount ratio, it has surprisingly been found that should
Drug has the function of significantly improving constipation symptom, while significant mitigate takes oil mark caused by orlistat, fatty stool
Adverse reaction achieves significant progress compared with prior art.
Specific embodiment
The specific embodiment of form by the following examples makees further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to following embodiment.
It is 1.14 × 10 by molecular weight involved in the present invention5u、4.23×105U and 6.01 × 105The konjac mannan of u
Oligosaccharide is respectively designated as KOGM-1, KOGM-2, KOGM-3.The preparation of the konjac mannan oligosaccharide of three kinds of molecular weight refers to
[rheological behavior of different molecular weight konjac mannan oligosaccharide, the superfine chemical industry progress of the rigid Korea Spro's sheet of Yao Xue Luo Xue].
Embodiment 1, orlistat and konjac mannan oligosaccharide tablet
Prescription 1:
| Ingredient | Dosage (g/ piece) |
| Orlistat | 0.045g |
| Konjac mannan oligosaccharide | 0.45g |
| Microcrystalline cellulose | 1.365g |
| Lauryl sodium sulfate | 0.18g |
| Sodium Starch Glycolate | 0.36g |
| Polyvinylpyrrolidone | 0.3g |
| Magnesium stearate | 0.3g |
| It is total | 3.0g |
Wherein, konjac mannan oligosaccharide is made of 12wt%KOGM-1,65wt%KOGM-2 and 23wt%KOGM-3.
Prescription 2:
| Ingredient | Dosage (g/ piece) |
| Orlistat | 0.105g |
| Konjac mannan oligosaccharide | 0.6g |
| Microcrystalline cellulose | 1.2g |
| Lauryl sodium sulfate | 0.195g |
| Sodium Starch Glycolate | 0.3g |
| Polyvinylpyrrolidone | 0.3g |
| Magnesium stearate | 0.3g |
| It is total | 3.0g |
Wherein, konjac mannan oligosaccharide is made of 22wt%KOGM-1,50wt%KOGM-2 and 28wt%KO GM-3.
Prescription 3:
Wherein, konjac mannan oligosaccharide is made of 8wt%KOGM-1,60wt%KOGM-2 and 32wt%KOGM-3.
1~3 preparation method of prescription:
Orlistat, konjac mannan oligosaccharide, microcrystalline cellulose and the Sodium Starch Glycolate of corresponding amount are taken, mixing is equal
It is even, obtain medicinal powder；Lauryl sodium sulfate and polyvinylpyrrolidone are dissolved in pure water, mixed with above-mentioned medicinal powder, is granulated, is squeezed,
It is dry, be added magnesium stearate, tabletting to get.
1~5 orlistat of comparative example and konjac mannan oligosaccharide tablet
Comparative example 1: comparative example 1 and the difference of prescription 1 are that konjac mannan oligosaccharide is 100wt%KOGM-1.
Comparative example 2: comparative example 2 and the difference of prescription 1 are that konjac mannan oligosaccharide is 100wt%KOGM-2.
Comparative example 3: comparative example 3 and the difference of prescription 1 are that konjac mannan oligosaccharide is 100wt%KOGM-3.
Comparative example 4: comparative example 2 and the difference of prescription 1 are that konjac mannan oligosaccharide is by 5wt%KOGM-1,62wt%
KOGM-2 and 35wt%KOGM-3 composition.
Comparative example 5, orlistat tablets
Comparative example 5 and the difference of prescription 1 are, are added without konjac mannan oligosaccharide.
Test example one, pharmacodynamics test
1.1 experimental animals: adult female rats, weight 18~22g, every group 15.
The grouping of 1.2 dosage and given the test agent give the time: mouse is randomly divided into model control group, Normal group, group
Test medicine is given using administration by gavage by 1 group and 1~5 group of comparative example of side, and stomach-filling amount is 0.5ml/20g, removes Normal group and mould
Outside type control group, 1 group of prescription and 1~5 group of comparative example give each group rat corresponding drug 7d by the dosage of 60mg/kg, normally
Control group and model control group give the distilled water of equal volume.
1.3 modelings: after giving given the test agent 7d, fasting 16h, in addition to Normal group, the oral stomach-filling of remaining each group is given
Modeling medicaments compound diphenoxylate (10mg/kg), establishes Constipated mice.
1.4 index determining methods: after compound diphenoxylate stomach-filling 0.5h, model control group, Normal group prepared Chinese ink
Stomach-filling, 1 group of prescription, 1~5 group of comparative example give the prepared Chinese ink containing relative medicine, the equal single cage raising of animal, and normal water is fed,
Since filling prepared Chinese ink, records every animal first grain row's melena time, arranges melena grain number in 6h and weight, stool weight and aqueous
Amount variation.
2. test result
2.1 rats arrange melena time, 6h defecation frequency for the first time
1 rat of table arranges melena time, 6h defecation frequency for the first time
| Group | First just time/min | Arrange melena number |
| Normal group | 90.54±12.35 | 7.53±1.20 |
| Model control group | 189.62±32.66** | 5.27±1.08** |
| 1 group of prescription | 116.70±18.12## | 9.36±2.21## |
| 1 group of comparative example | 165.44±22.53 | 6.18±2.54 |
| 2 groups of comparative example | 166.49±15.83 | 5.93±1.36 |
| 3 groups of comparative example | 162.62±30.31 | 6.08±1.59 |
| 4 groups of comparative example | 128.03±25.95## | 8.55±2.33## |
| 5 groups of comparative example | 172.55±29.58 | 6.21±1.32 |
Note: compared with Normal group,**P < 0.01,*P < 0.05；Compared with model group,##P < 0.01,#P < 0.05.
2.2 6h defecation weight and water content
2 6h defecation weight of table and water content
| Group | Grain number/grain | Excrement gross weight (g) | Water content (%) |
| Normal group | 20 | 0.36±0.12 | 61.25±15.35 |
| Model control group | 20 | 0.12±0.06** | 38.73±12.16** |
| 1 group of prescription | 20 | 0.54±0.14## | 66.84±20.44## |
| 1 group of comparative example | 20 | 0.18±0.10 | 42.03±8.40 |
| 2 groups of comparative example | 20 | 0.14±0.09 | 39.69±16.44 |
| 3 groups of comparative example | 20 | 0.20±0.04 | 46.87±12.21 |
| 4 groups of comparative example | 20 | 0.39±0.11## | 59.37±10.38## |
| 5 groups of comparative example | 20 | 0.16±0.03 | 48.32±14.27 |
Note: compared with Normal group,**P < 0.01,*P < 0.05；Compared with model group,##P < 0.01,#P < 0.05.
By upper table 1,2 it is found that compared with Normal group, model group rats head just time, 6h defecation frequency and weight, excrement
Just there is significant difference (P < 0.01) in change of moisture content, illustrate modeling success.Wherein, compared with model group, medicine of the present invention
Object can significantly shorten the big mouse's head of Constipation Model just time, increase rat 6h defecation frequency and weight, excrement water content, with model group
With significant difference (P < 0.01), it is practicable for showing that drug of the present invention is used to treat constipation.And from comparative example 1~
3 groups of test results, which can be seen that, only to be combined to constipation with orlistat without bright by a kind of konjac mannan oligosaccharide of molecular weight
Aobvious treatment effect, indices are compared with model group without significant difference.
Test example two, clinical test
2.1 test groupings: random by the constipation symptom (defecation frequency, fecal character, symptom duration etc.) of subject
It is divided into 1 group of prescription, 1~4 group of comparative example and positive controls, every group of 60 subjects.
2.2 given the test agent dosage and application method:
1 group of prescription, 1~4 group of comparative example (oral dose is 120mg tid) and positive controls (placebo) are oral corresponding
Drug, tested by blind, given the test agent gives time 7d.
The observation of 2.3 constipation symptoms
2.3.1 daily stool interval (d/ times): I grade (0 point): 1~2；II grade (1 point): 3；III grade (2 points): 4~5；IV grade
(3 points): > 5
2.3.2 defecation condition: it is divided into I~IV grade according to difficult defecation degree, counts integrated value:
I grade (0 point): defecation is normal；II grade (1 point): only bearing down, sense of discomfort；III grade (2 points): bearing down, sense of discomfort
Obviously, or there are just frequency but difficult defecation and measure less, it is less abdominal pain or anus burn feeling occur；IV grade (3 points): abdominal pain often occur
Or anus burn feeling, influence defecation.
2.3.3 fecal character: fecal character is divided into I~III grade according to Bristol fecal character classification, statistics product
Score value:
I grade (0 point): smooth and soft as sausage or snake；As sausage, but on its surface by slight crack；Soft agglomerate, has
Apparent edge (being easily drained)；II grade (1 point): sausage shape, but have agglomerate；Loose bulk, edge roughness, as muddy
Excrement；III (2 points): the hard group of separation, as fruit stone (being not easy to be discharged)
2.3.4 orlistat adverse reaction is investigated: record and is counted whether there is or not there is oil mark and fatty stool adverse reaction
There is the number of above-mentioned adverse reaction.
3. result
3.1, which take front and back constipation symptom mean scores, compares
Table 3 takes front and back constipation symptom mean scores result
Note: compared with before medication,**P < 0.01,*P < 0.05.
As upper table 3 it is found that 1 drug of prescription can significantly mitigate the reduction of defecation frequency caused by constipation, difficult defecation, excrement
The symptoms such as dry and hard, and comparative example 1~3, without apparent improvement result, comparative example 4 shows significant increase in test example one
The effect of rat 6h defecation frequency and weight, excrement water content, in the investigation of above-mentioned constipation symptom, in defecation frequency and excrement
On characteristic index with significant difference is all had before medication, but in terms of defecation condition, take front and back no significant difference, therefore
No significant difference before leading to final total symptom mean scores and taking medicine.
Situation statistical result is investigated in 3.2 orlistat adverse reactions
There is adverse reaction demographics result after 4 60 patient's medications of table
| Grouping | Oil mark | Fatty stool |
| 1 group of prescription | 0 | 0 |
| 1 group of comparative example | 0 | 1 |
| 2 groups of comparative example | 1 | 0 |
| 3 groups of comparative example | 1 | 2 |
| 4 groups of comparative example | 0 | 0 |
| 5 groups of comparative example | 15 | 12 |
By upper table 4 it is found that after taking 1 drug of prescription of the present invention, it is bad anti-that oil mark, fatty stool does not occur in patient
It answers, and comparative example 1~4 has 1~2 patient above-mentioned adverse reaction occur.And 5 groups of comparative example (it is oligomeric to be added without konjac mannan
Sugar) there are 15 oil spot phenomenon occur in 60 patients, there is fatty stool in 12 patients, this explanation, konjac mannan
Oligosaccharide can significantly reduce oil mark caused by orlistat and fatty stool adverse reaction.
The above-described embodiments merely illustrate the principles and effects of the present invention, and is not intended to limit the present invention.It is any ripe
The personage for knowing this technology all without departing from the spirit and scope of the present invention, carries out modifications and changes to above-described embodiment.Cause
This, institute is complete without departing from the spirit and technical ideas disclosed in the present invention by those of ordinary skill in the art such as
At all equivalent modifications or change, should be covered by the claims of the present invention.
Claims (2)
1. a kind of drug for treating constipation, which is characterized in that the drug includes a effective amount of orlistat and a effective amount of point
Son amount is 1.14 × 105u、4.23×105U and 6.01 × 105The konjac mannan oligosaccharide of u, wherein the molecular weight is
1.14×105The konjac mannan oligosaccharide accounting of u is 8~22wt%.
2. drug as described in claim 1, which is characterized in that the drug is made of the raw material of following proportion:
The orlistat of 0.1~10% (w/w),
5~25% (w/w) have the konjac mannan oligosaccharide of different molecular weight, the Amorphophallus rivieri glucomannan with different molecular weight
Dew oligosaccharide includes that molecular weight is 1.14 × 105u、4.23×105U and 6.01 × 105The konjac mannan oligosaccharide of u, and molecule
Amount is 1.14 × 105The konjac mannan oligosaccharide accounting of u is 8~22wt%, and,
The pharmaceutically available auxiliary material of surplus.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810752410.XA CN108524495B (en) | 2018-07-10 | 2018-07-10 | Purposes of the orlistat in the drug of preparation treatment constipation |
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| CN201810752410.XA CN108524495B (en) | 2018-07-10 | 2018-07-10 | Purposes of the orlistat in the drug of preparation treatment constipation |
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| CN108524495B true CN108524495B (en) | 2019-02-26 |
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| CN112890196B (en) * | 2021-03-10 | 2022-04-22 | 江西仙客来生物科技有限公司 | Lucid ganoderma and rhizoma polygonati capsule and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649580A (en) * | 2002-04-26 | 2005-08-03 | 霍夫曼-拉罗奇有限公司 | Pharmaceutical composition comprising a lipase inhibitor and glucomannan |
| CN106822097A (en) * | 2017-03-10 | 2017-06-13 | 中山万汉制药有限公司 | A kind of pharmaceutical composition containing orlistat for losing weight |
| CN106924270A (en) * | 2017-03-10 | 2017-07-07 | 中山万汉制药有限公司 | A kind of pharmaceutical composition with weight losing function containing orlistat |
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2018
- 2018-07-10 CN CN201810752410.XA patent/CN108524495B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649580A (en) * | 2002-04-26 | 2005-08-03 | 霍夫曼-拉罗奇有限公司 | Pharmaceutical composition comprising a lipase inhibitor and glucomannan |
| CN106822097A (en) * | 2017-03-10 | 2017-06-13 | 中山万汉制药有限公司 | A kind of pharmaceutical composition containing orlistat for losing weight |
| CN106924270A (en) * | 2017-03-10 | 2017-07-07 | 中山万汉制药有限公司 | A kind of pharmaceutical composition with weight losing function containing orlistat |
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