CN1481796A - Medication for adiposity - Google Patents
Medication for adiposity Download PDFInfo
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- CN1481796A CN1481796A CNA031488331A CN03148833A CN1481796A CN 1481796 A CN1481796 A CN 1481796A CN A031488331 A CNA031488331 A CN A031488331A CN 03148833 A CN03148833 A CN 03148833A CN 1481796 A CN1481796 A CN 1481796A
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- berberine
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Abstract
The present invention relates to the application of high-solubility berberine in preparing medicine for preventing and treating obesity. The berberine includes berberine derivatives other than berbamine, and is easy to dissolve in water. The berberine is easy to absorb in human body and has high curative effect in eliminating excessive fat.
Description
Technical field
The present invention relates to the new purposes of berberine (except the berberine hydrochloride), relate in particular to the application of high-dissolvability berberine in medicines such as preparation treatment or prevent obesity.
Background technology
Both at home and abroad the control of obesity is very paid attention to.Overweight and obesity are the important roots that causes numerous disease, bring out or add the disease of re-correlation easily, as hypertension, hyperlipidemia, coronary heart disease, diabetes, myocardial infarction, cerebrovascular disease and some cancer etc.These diseases interact again, add fuel to the flames, and produce a series of complication, serious harm patient's health and life-span.President doctor Louis of United States Medicine community points out: " cancer is fearful, but what human health was caused biggest threat is fat." World Health Organization (WHO) was defined as a kind of disease to obesity in Genevangenevese meeting 1997 years.
The method of preventing and treating obesity is a lot, and the medicine that wherein is used to lose weight mainly contains the central appetite suppressant, absorbs Inhibitors, sugar utilizes Western medicine and some Chinese medicine, Chinese patent medicine and Chinese medicine and western medicine compound preparations etc. such as promoter, diuretic, fever agent, hypoglycemic agent.Though they have certain effect to losing weight, many drug side effectes are more, and are that have even relatively more serious, and it is few really fundamentally to reduce the medicine (or product, food) of body fat.
In the clinical observation of using high-dissolvability berberine treatment diabetes; patient's effective blood sugar lowering (applying for a patent separately) after taking berberine sulphate; simultaneously unexpectedly find that some overweight people's body weight alleviate naturally, reduce to normal gradually or near normal level.
Berberine another name berberine is an isoquinoline alkaloid, is the active ingredient of plant such as Rhizoma Coptidis.The Rhizoma Coptidis total alkaloids that obtains from Chinese medicine extraction such as Rhizoma Coptidis mainly contains berberine hydrochloride (berberine hydrochloride), citric acid berberine (citric acid berberine), hydrogen sulfate berberine (hydrogen sulfate berberine), berberine sulfate (berberine sulphate) and phosphoric acid berberine (phosphoric acid berberine) through further isolated monomer berberine.
The dissolubility difference of various berberine very big (seeing Table 1).International new drug research person pays much attention to the important function of biopharmaceutics categorizing system (BCS) in the medicament research and development process in recent years.BCS is divided into four classes to medicine according to the height of the membrane permeability of its dissolubility and intestinal, high-dissolvability is classified as the primary standard of first kind medicine.The most dissolubility of Chinese medicine is lower, and membrane permeability is higher, belongs to the second class medicine among the BCS.Former chairman of American Pharmaceutical Association points out, the discovery of medicine and research worker will be paid close attention to the situations such as dissolubility of medicine from the beginning, thereby before can avoiding the later stage clinical and the failure of clinical research, the success rate (Chinese Medicine of improving new drug development, 2002.8.10,8 editions).Therefore, the height of berberine dissolubility too can be directly has very important influence to the size of its bioavailability and range of application and clinical efficacy.
The part berberine was once produced injection as the human antimicrobial drug, because of meeting generation serious adverse reaction, even the causing death.For this reason, the berberine injection is disabled before more than ten years.So far after this, people still take berberine hydrochloride (as the berberine hydrochloride sheet of Zhongyi Pharmaceutical Industry Co., Ltd's production) for a long time, but its dissolubility is very little, and oral absorption is very poor, and blood drug level is very low, only is used for antibiotic.Though the higher berberine of other several dissolubility is soluble in water, oral absorption is good, but the drug effect of giving full play to, but only make antimicrobial drug for animals (the berberine sulphate injection for animals of producing as Jiangxi people's star animal health product company limited) or make chemical reagent.Country expressly provides: people's medicine, veterinary drug must strictly separate, forbid using with; Chemical reagent does not belong to medicine, must not be used for medical treatment.Up to now, oral " berberine " in clinical use and pharmacy's sale all is single berberine hydrochloride.Therefore, human " berberine " taken for a long time be berberine hydrochloride in fact still, does not comprise other berberine as veterinary drug and reagent etc." berberine " that it has often been said only is the abbreviation to berberine hydrochloride, then indicates its full name on medical books and periodicals and this drug package thing.For a long time, medicinal berberine signs at state-promulgated pharmacopoeia or Arzneibucs or veterinary drug standard or this medicine bottle that all only to state clearly be that " antimicrobial drug is used for intestinal infection." even the pharmacy corporation of producing various berberine in the operation instruction of its product (crude drug or people, animal medicine etc.) and the scope of application except antibiotic the purposes of all not mentioned human treatment's of can be used for obesity and other disease.
Write articles according to burnt Wan Tian etc.: " berberine be it is generally acknowledged and had no side effect.On present data, what cause untoward reaction is not berberine tablet but injection.It is dead that the oral a large amount of berberines of zoopery are unlikely." (adverse reaction of tcm and treatment, People's Medical Officer Press, 1996,39～42).Write articles according to another Wang Yongyi etc.: " berberine is by China's at first synthetic success in the world.Maximum characteristics are that side effect is little, for side effect reckling in the antibacterials, main organs such as liver, kidney, skeleton and nervus centralis are had no adverse effects." (Golden Shield publishing house, 1991,36～37 are asked in the sick control 320 of common transmittable).Write articles according to the Xie Hui people again: " berberine is a kind of bitter tonic, can stimulate gastric secretion, facilitating digestion.Can make the fatty emulsifying of eating into, evenly be absorbed, turn round, distribute by gastrointestinal and be utilized digestion." (the Shenyang evening paper, 1995.6.24)
According to above-mentioned situation, can find several rules:
1. present, no matter be that human or berberine for animals all belong to the anti-microbial type medicine, all be not used for the treatment of obesity and other medical application.
2. what be used for human body has only the very low berberine hydrochloride of dissolubility, illustrates that what use in clinical practice and experimentation also is berberine hydrochloride.
3. to berberine, patient's suitable for oral administration is forbidden injection; Animal is then opposite: unsuitable oral, be suitable for injection.
4. the dissolubility of berberine is high more, and bioavailability is big more, and pharmacological action is strong more, and therapeutic effect is good more.
5. the human berberine of only taking low solubility, beasts are used the berberine of high-dissolvability entirely.
Article 5, in In the view of today the very inequitable phenomenon and the mankind can not take the formed technology prejudice of veterinary drug and continued decades so far, cause people not go to consider that animal drugs is used for the treatment of the probability of human body diseases, hinder the research and development of people for a long time this technical field.If high-dissolvability berberine such as berberine sulphate for animals are improved dosage form, be prepared as the human oral drug, greatly change the route of administration of this material, the bioavailability of its active substance is improved, toxicity reduces, stability increases, and the dissolubility that adds them has improved manyfold than the berberine hydrochloride of human, can promote drug absorption, give full play to drug effect, impel curative effect to increase substantially, can enlarge medical application thus, be widely used in multiple diseases such as treatment and prevent obesity.
Summary of the invention
The object of the present invention is to provide the new purposes of other berberine in the medicine of preparation treatment or prevent obesity and some other disease except berberine hydrochloride.Described berberine also comprises the berberine of high-dissolvability and the above-mentioned berberine of citric acid berberine, hydrogen sulfate berberine, berberine sulfate and phosphoric acid berberine and extraction from plant, chemosynthesis or the acquisition of other method.
The berberine of described high-dissolvability be meant can be in less than 500 parts of (weight) water dissolved berberine, preferred berberine is that the dissolubility in water is 1: 100 (weight), preferably 1: 30 (weight), 1: 15 even (weight).
In fact, the present invention relates to the application of high-dissolvability berberine in preparation treatment or prevention of obesity disease drug.
The specific embodiment:
In one embodiment of the invention, described berberine also can obtain through chemosynthesis and other method except extracting from plant.
In another embodiment of the invention, select any or two or more other berberine except berberine hydrochloride for use or adopt high-dissolvability (can be dissolved in less than 500 parts of water) berberine (comprising citric acid berberine, hydrogen sulfate berberine, berberine sulfate and phosphoric acid berberine) crude drug powder to be prepared into medicine according to a conventional method; The medicine that also can use any or two or more above-mentioned berberine crude drug or its preparation and other any material (medicine or pharmaceutics acceptable auxiliary component) to make up according to a conventional method or prepare is used for the treatment of or prevent obesity.Its preparation is the described any dosage form except injection of pharmaceutics---comprising capsule and tablet, each oral berberine 0.3～1.2g that is grown up took at whenever 2 hours before the meal every day 3 times, and severe overweight people adds once before sleeping evening.General 2～4 months of the course of treatment, heavier overweight people's administration time takes the circumstances into consideration to prolong.
In order to understand essence of the present invention better, the result with using sulfated berberine treatment of obesity illustrates its new purposes in pharmaceutical field below.
Criterion about obesity, understand the introduction of obesity research association according to Chinese health science, general internationally recognized standard is: (height centimetre-100) * 0.9 is standard body weight (kilogram), surpassing this standard 20% just constitutes fat, surpass 40% be exactly more serious obesity (Chinese newspaper cutting, 2000.5.19).
Embodiment 1
Antiobesity action to diabetics
Use 35 routine patients of high-dissolvability berberine treatment type 2 diabetes mellitus, on the basis of keeping on a diet, take berberine sulfate capsule (every 0.3g), everyone obeys 1～4 (measuring increase gradually from minimum) at every turn, every day 3 times, takes at whenever 2 hours before the meal.Blood glucose reduce to normal after, find that wherein 9 overweight persons body weight under the situation of not using any method of weight-reducing or medicine slowly drops to normal or a little more than normal level.As first take the type 2 diabetes mellitus patient Wu of veterinary drug berberine sulfate * *, the man, height 170cm, body weight slowly descends naturally in the normal back of blood sugar recovery, reduces to 70kg from original 81.5kg, minimizing 11.5kg.Amount of decrease 14.11%; Waistline is reduced into 90cm from 105cm, reduces 15cm.Particularly the abdominal part of original conceived shape dwindles significantly, and original hypertension is reduced to normal range, and the blood T-CHOL significantly reduces, transference cure such as arrhythmia, uncomfortable in chest and numb pain of brothers.After this, body weight and waistline do not continue to reduce again, and also bounce-back is not risen, and remains on preferable states for a long time.Fat-reducing effect in various degree appears in the diabetics of other 8 obesities too.
At that time, may be because of suffering from due to the diabetes to these phenomenon analysis of losing weight, but can not get rid of the effect of medicine.In order further to seek definite reason, selected the overweight person of some non-diabetics afterwards successively, repeat to do this test.
Embodiment 2
Observation of curative effect to general overweight people
Select overweight person 8 people do not suffer from diabetes or other disease, severe obesity (body weight＞standard body weight 40% above person) 1 people wherein, moderate obesity (body weight＞standard body weight 30～39%) 2 people, slight obesity (body weight＞standard body weight 10～29%) 5 people.
These overweight persons all by the oral berberine sulfate capsule of the usage and dosage of embodiment 1, suitably control the dietary habit of eating and drinking extravagantly originally simultaneously, take that body weight begins to descend gradually after 2～3 months, but amplitude is had nothing in common with each other.
As overweight people Lee * *, the woman, height 158cm, body weight 73.5kg, take berberine sulfate after, body weight is reduced to 60.5kg gradually, reduces 13kg, amount of decrease 17.69%, waistline is contracted to 77cm from 91cm, reduces 14cm.Abdominal circumference, hip circumference obviously reduce, and blood pressure, blood fat and life, work capacity recover normal.
The overweight person of the diabetics of the foregoing description 1 and example 2 and non-diabetic is totally 17 people, produces fat-reducing effect in various degree after taking berberine sulfate mostly.Wherein: produce effects (amplitude that loses weight＞10%) 9 examples account for 52.94%; Effectively (amount of decrease 3～10%) 6 examples account for 35.29%; Invalid (amount of decrease＜3%) 2 examples account for 11.77%; Total effective rate 88.23%.Following characteristics appear simultaneously:
1, the fat more person's fat-reducing effect of build is obvious more.
The position of 2, losing weight mainly is the superabundant fats that abdominal part is piled up.
3, weight loss speed is slow, and amplitude is less.The routine number that can reduce to standard body weight is less, keeps stable when reducing to about height-100 (a little more than standard body weight) mostly, and this moment, body weight seldom continued to descend, and rise does not rebound yet.
4, behind the weight loss, originally blood pressure, blood fat the higher person are reduced to normally thereupon, and fat thickness reduces, and vital capacity raises, and asthma in the time of upstairs, effort phenomenon disappear, and feel good.
The slimming medicine of the high-dissolvability berberine preparation that the present invention uses also has following beneficial effect:
1, safety of medicine is efficient: these berberine are soluble in water, can be absorbed fully by body, so blood drug level increases, bioavailability improves thereupon, can give full play to drug effect, on curative effect, surpass berberine hydrochloride commonly used significantly, particularly berberine sulphate is improved to oral formulations, the serious adverse reaction that can avoid administrated by injection to bring is taken as safe as a house.
2, meet quality standard: they are to the determined curative effect of obesity, steady quality, and side effect is slight.Get owing to its raw material adopts single medicinal material to extract, effective ingredient is clear, and effect clearly has controlled quality standard, meets the international quality standards of " safe, effective, controlled, stable " that medicine should possess, also is the unitary basis of the modernization of Chinese medicine.
3, desirable slimming medicine: they can reduce to normal or near after normal in overweight people's body weight; stable for extended periods of time; do not see the body weight rise; unhealthful abnormal phenomena does not appear; the principle that meets the fat-reducing of international medical science---" not anorexia, do not suffer from diarrhoea, not weak "; in addition, can also reach and do not rebound.
The invention has the advantages that:
1, the present invention has excavated new medical usage to high-dissolvability jamaicins such as veterinary antibacterial and chemical reagent, opens Opened up many-sided application prospect.
2, the present invention medicine material source of using is abundant, preparation technology is simple, low production cost, pharmacological action very By force, bad reaction is slight, range of application is wide. There are the various jamaicins of production in the beautiful prosperous pharmaceutcal corporation, Ltd in Sichuan Province.
The main jamaicin overview table of table 1.
| The bulk drug title | Solubility in water | Purposes | |
| Berberine hydrochloride (Halomine) | 1∶500 | Low | 1. human or antimicrobial for animals, Be used for enteric infection. 2. chemical reagent. |
| Citric acid jamaicin (citric acid berberine) | 1∶125 | High | |
| Berberine bisulfate (Berberine bisulfate) | 1∶100 | ||
| Berberine sulfate (berberine sulphate) | 1∶30 | ||
| Phosphoric acid jamaicin (phosphoric acid berberine) | 1∶15 | ||
Annotate: (1) dissolubility data draws from " Chemistry for Chinese Traditional Medicine ", the Wu Lijun chief editor, and Yan Liu's literary composition is write articles, and Chinese Medicine science and technology is published Society, 2001,48.
(2) standard of Berberine solubility height of the present invention is with the dissolubility data of human drugs Berberine hydrochloride in water Be the line of demarcation.
(3) high-dissolvability jamaicin of the present invention refers to the various jamaicins that can dissolve in less than 500 parts of water.
According to " the reagent handbook (compile, and the Shanghai science and technology is published by China Drug Co.'s Solution on Chemical Reagents in Shanghai purchasing and supply station Society publishes, in November, 1985 second edition) the 178th, 179 page of record, the Berberine bisulfate of chemical synthesis, sulfuric acid Jamaicin also can be used for checking the chemical reagent of nitrate etc. Its structural formula and relevant being described as follows: Berberine disulfate Berberine sulfate Berberine bisulfate Berberine sukfate
C
20H
19NO
8S＝433.43 C
40H
36N
3O
12S·3H
2O=822.83 [another name] jamaicin disulfate, the jamaicin bisulfate; [another name] jamaicin sulfate, berberine sulphate
Acid b3rberine sulfate， Neutral berberine sulfate
Berberine hydrogen sulfate, [proterties] yellow acicular crystal. Can be dissolved in alcohol and 30 fens water, hardly
Berberine hemisulfate is dissolved in ether, benzinum and chloroform. [proterties] yellow acicular crystal. Can be dissolved in about 100 minutes water, [purposes] check nitrate and fluorescence microscopic analysis.
Be slightly soluble in alcohol. [storage] sealing is preserved. [purposes] check nitrate. [storage] sealing is preserved.
Claims (6)
1. the application of high-dissolvability berberine in preparation treatment or prevention of obesity disease drug, it is characterized in that: described berberine is other berberine except berberine hydrochloride.
2. application according to claim 1 is characterized in that: described berberine be can be in less than 500 parts of water dissolved berberine---comprising citric acid berberine, hydrogen sulfate berberine, phosphoric acid berberine with now be the berberine sulfate of veterinary drug or reagent.
3. application according to claim 1 and 2 is characterized in that: described berberine comprises from plant and to extract or berberine that chemosynthesis obtains.
4. application according to claim 3 is characterized in that: described berberine is the medicine of single berberine or the combination of two or more berberine.
5. application according to claim 4 is characterized in that: described medicine is any dosage form except injection.
6. application according to claim 5 is characterized in that: described dosage form comprises the various peroral dosage forms of capsule, tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031488331A CN1481796A (en) | 2003-06-13 | 2003-06-13 | Medication for adiposity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031488331A CN1481796A (en) | 2003-06-13 | 2003-06-13 | Medication for adiposity |
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| Publication Number | Publication Date |
|---|---|
| CN1481796A true CN1481796A (en) | 2004-03-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031488331A Pending CN1481796A (en) | 2003-06-13 | 2003-06-13 | Medication for adiposity |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITVA20090037A1 (en) * | 2009-06-19 | 2010-12-20 | Alphrema Srl | COMPOSITIONS FOR THE TREATMENT OF SUBJECTS THAT PRESENT AN EXCESS OF ADIPOSE FABRIC, ALSO LOCALIZED, EVENTUALLY ASSOCIATED WITH DISORDERS OF GLUCID AND / OR LIPID METABOLISM |
| FR2987270A1 (en) * | 2012-02-29 | 2013-08-30 | Agronomique Inst Nat Rech | COMBINATION PRODUCT FOR TREATING OVERWEIGHT AND / OR IMPROVING SILHOUETTE |
| CN103356611A (en) * | 2013-06-24 | 2013-10-23 | 上海交通大学医学院附属瑞金医院 | Application of berberine in preparation of weight-loss drug |
| CN108635351A (en) * | 2018-04-19 | 2018-10-12 | 上海华堇生物技术有限责任公司 | The medicinal usage of berberine sulphate |
-
2003
- 2003-06-13 CN CNA031488331A patent/CN1481796A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITVA20090037A1 (en) * | 2009-06-19 | 2010-12-20 | Alphrema Srl | COMPOSITIONS FOR THE TREATMENT OF SUBJECTS THAT PRESENT AN EXCESS OF ADIPOSE FABRIC, ALSO LOCALIZED, EVENTUALLY ASSOCIATED WITH DISORDERS OF GLUCID AND / OR LIPID METABOLISM |
| FR2987270A1 (en) * | 2012-02-29 | 2013-08-30 | Agronomique Inst Nat Rech | COMBINATION PRODUCT FOR TREATING OVERWEIGHT AND / OR IMPROVING SILHOUETTE |
| WO2013128137A1 (en) * | 2012-02-29 | 2013-09-06 | Institut National De La Recherche Agronomique - Inra | Combination product for treating excess weight and/or for improving the figure |
| CN103356611A (en) * | 2013-06-24 | 2013-10-23 | 上海交通大学医学院附属瑞金医院 | Application of berberine in preparation of weight-loss drug |
| CN108635351A (en) * | 2018-04-19 | 2018-10-12 | 上海华堇生物技术有限责任公司 | The medicinal usage of berberine sulphate |
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