CN1460472A - Biquanide vanadium complex plaster preparation for curing diabetes and its application - Google Patents
Biquanide vanadium complex plaster preparation for curing diabetes and its application Download PDFInfo
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Abstract
The present invention relates to a medicine plaster biguanide vanadium complex for curing diabetes. Said invention active complex contains biguanide chelating agent, and it also contains transdermal absorption accelerant, transdermal absorption permeation adjuvant and softening agent.
Description
Technical field
The invention belongs to the treatment diabetes medicament, be specifically related to a kind of patch and application thereof for the treatment of diabetes medicament biguanide vanudium complex.
Background technology
Non-insulin-dependent diabetes mellitus (Non-insulin dependent diabetes mellitus, be called for short NIDDM) is a kind of metabolic pattern disease, influenced by it at the population (wherein 10% people is more than 70 years old) of western countries nearly 5%～7%.It is feature with the hyperglycemia and often is attended by many other symptoms, comprises hypertension, obesity and lipid imbalance.Potential pathology is that the beta cell function that causes of unknown cause is impaired.Insulin resistant prior to the also glucose tolerance of predictive of impaired, may be the not normal reason of beta cell, and perhaps it may only disclose the existence of a main beta cell defective.
Existing treatment is substantially all based on oral or injectable drug.
Oral drugs have many defectives, and medicine is subjected to the influence of gastrointestinal tract physiologic factor, and single administration can not be kept the blood drug level of long period; The influence of liver " first pass effect ", the influence of metabolism amplitude, bioavailability is not too high, and side effect is obvious.
Simultaneously following document is mentioned, the complex that forms between vanadium and biguanide can blood sugar lowering, blood fat reducing, and can prevent the complication of diabetes:
1.Chakraborty?and?Das(1989)Analytica?Chimica?Acta?218：341-344；Syamal(1983)；
2.Ind?J.Pure?&?Applied?Phys.21：130-132；Calatayud?et?al.(1981)；
3.Afinidad?XXXVIII：537-540；Babykutty?et?al.(1974)；
4.Thermochimica?Acta?8：271-282；
5.Ray(1961)Chem.Rev.61：313-359。
External vanadate ion (VO
4 3-) the para-insulin effect be found (Nature 284:556-558[1980]) from 1980, what thought at that time that para-insulin promotes glucose oxidase in Adips Mus fat cell is the vanadyl ion.In 1985, McNeill et al. (1985) Science 227:1474-1477 has reported when drinking when taking, and vanadate has reduced the blood glucose that raises, prevented to utilize the reduction of the diabetic mice cardiac performance that chain urea bacterium (Streptozotocin, be called for short STZ) element causes.After Sakurai et al. (1980) Biochem.Biophys.Res.Comm.96:293-298 disclosure vanadate is reduced into vanadyl in vivo, just take much count of the imitation insulin effect of vanadate and vanadyl.
McNeill et al. (sees Am.J.Physiol 257:H904-H911 (1989), Metabolism 38:1022-1028 (1985), Diabetes 38:1390-1395 (1989) and Can.J.Physiol﹠amp; Pharmacol.68:486-491 (1990); No. the 5527790th, United States Patent (USP); No. 5300496) work disclose and vanadyl to be come oral as vanadium oxysulfate or maltol vanadyl complex, reduced the blood glucose and the blood fat of STZ diabetic mice, prevented second complication such as the cataract and the core function abnormality of diabetes.
US 6,287, and 586 provide the preparation method of the main active related compound that the present invention mentions, and to utilizing the therapeutic activity of the diabetic mice that streptozotocin (Streptozotocin is called for short STZ) causes.
Summary of the invention
The objective of the invention is to utilize transdermal therapeutic system (Transdermal Therapeutic System; Abbreviation TTS) advantage proposes a kind of new approaches to treatment of diabetes, promptly a kind of patch and application thereof for the treatment of diabetes medicament biguanide vanudium complex.
Technical scheme of the present invention is: develop a kind of patch for the treatment of diabetes medicament biguanide vanudium complex, it is characterized in that:
(1) contain in this medicine patch structure as shown in the formula chemical compound as main active
R wherein
1And R
2Be selected from H, methyl, ethyl, propyl group, isopropyl, butyl, cycloalkyl, phenyl or phenethyl respectively;
Activated complex comprises the biguanide chelating agen, and the biguanide chelating agen of preferred 1 replacement can form a hexa-atomic unsaturated vanadium containing ring by the chelating vanadium; Vanadium in the complex and oxygen, sulfur or nitrogen coordination are preferably with the oxygen coordination;
(2) in this medicine patch, except that containing the main active for the treatment of effective dose, also contain Percutaneous absorption enhancer, transdermal absorption penetration promoter and softening agent.
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said principal agent is 1,1-dimethyl biguanide vanudium complex;
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said principal agent are 1-phenformin vanudium complexs;
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said principal agent are 1-butyl biguanide vanudium complexs;
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said vanadium are to exist with V (IV) or V (V) form;
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said Percutaneous absorption enhancer is laurocapram, Mentholum, Borneolum Syntheticum or Oleum Eucalypti, the mixture of wherein one or more;
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said transdermal absorption penetration promoter is ethanol, propanol, butanols or propylene glycol, the mixture of wherein one or more;
The patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, wherein said softening agent is glycerol, polyvinyl alcohol, polyvidon or lanoline, the mixture of wherein one or more;
The purposes of the patch of above-mentioned treatment diabetes medicament biguanide vanudium complex, it is characterized in that except that the medicinal usage of preparation treatment diabetes, can also be used to prepare the purposes of blood pressure lowering preparation, obesity appetite suppressant and hypercholesterolemia, high triglyceride adjusting preparation.
Transdermal therapeutic system (TTS) is a kind of novelty, feasible, pharmaceutical preparation that suitable potentiality are arranged, has now become one of central topic of third generation formulation development research; Be called as " third generation preparation ", have wide tempting prospect.
Existing transdermal therapeutic system can be divided into: 1. membrane controlled release type (Membrane Permeation-Controlled), 2. framework controlled release type (Matrix Doffusion-Controlled), 3. decentralized (Adhesive Dispersion Type) in small storage storehouse dissolving control release type (MicroreservioirDissolusion-Controlled) or 4. binding agents.
Effective ingredient enters the approach of subcutaneous blood capillary, has by intercellular substance to penetrate, and comprises the passage of hair follicle, sebaceous gland, sweat gland through the accessory organ.But if change its fat-soluble or assisting down at corresponding percutaneous absorption fortifier by liposome, can effectively overcome the barrier of keratin filament and lipid in the keratodermatitis, make more composition infiltrate cortex, enter sanguimotor process, reach certain blood drug level or reach certain local concentration, thereby reach the therapeutic purposes of whole body drug effect.
The present invention is development and the extension to above-mentioned United States Patent (USP) (US 6,287,586), has proposed the relevant concrete preparation of preparation, specifically is a kind of patch for the treatment of diabetes medicament biguanide vanudium complex.
Advantage of the present invention is:
1. can avoid oral administration, medicine is subjected to the influence of gastrointestinal tract physiologic factor and liver " first pass effect ", and absorption, metabolic individual difference are less; The metabolism amplitude reduces, the bioavailability height, and side effect alleviates relatively;
2. can provide treatment needed, near the rate of releasing drug of zero level; Easy to use, patient is easy to accept and can remove drug-supplying system at any time, stops administration.
Description of drawings
Fig. 1 is the state that vfanadium compound reduces the glucose ability in the diabetic mice body, the comparison procedure of Yan Shening in time;
Fig. 2 is the area under curve of Fig. 1, and a total comparison is provided.
The specific embodiment
The application provides the preparation of following patch as embodiment; but be not limited to the scope that application documents are mentioned; can extend fully and dissolve the patch of decentralized in control release type or the binding agent to known membrane controlled release type, framework controlled release type, small storage storehouse; the applicant thinks main active that every the present invention of containing points out and be used for the treatment of the patch and the equivalent thereof of non-insulin-dependent diabetes mellitus (NIDDM) and relevant disease purposes thereof all should belong to the protection domain of this patent.
The skin that is covered with body surface only has 3mm thick, but is tissue maximum in the human body, and skin is the barrier together between external environment and the body.Percutaneous absorption enhancer means the speed that can accelerate the medicine transdermal and the material that skin is not formed serious stimulation and infringement.The mechanism of action of penetration enhancer mainly is to change skin texture by reversibility to penetrate into skin and reduce medicine through the suffered resistance of skin, reaches the purpose that promotes absorption of medicine whole body or topical therapeutic.
Natural penetration enhancer such as book lotus brain, Borneolum Syntheticum, Oleum Eucalypti etc. are usually used in the preparation for external application to skin, local antipruritic, the refrigerant and slight local anesthetic action of performance.It has remarkable transdermal enhancing effect discovered in recent years; Most representative in the synthetic penetration enhancer is laurocapram (azone Azone), can accelerate the drug transdermal infiltration rate and skin is not caused the transdermal enhancer of serious stimulation and infringement and is subjected to extensive concern and application as a kind of.Be characterized in all having better short running to use to many hydrophilic, oleophylic synthetic drugs.The mechanism of action may be that lipoids produces main irregular arrangement and dissolves the purpose that the skin lipoids reaches increases drug absorption in the keratodermatitis by making.Modern medicinal agents research is thought.Transdermal administration not only will play local therapeutic effects, and will be through the effect of skin administration performance whole body therapeutic; Good synergism is also arranged between penetration promoter such as propylene glycol, ethanol etc. and the penetration enhancer.Softening agent can increase the flexibility of the permeability and the medicine film of medicine, promotes the absorption of medicine; Binary or polynary penetration enhancer tend to obtain than the better effect of single penetration enhancer sometimes.
Embodiment 1
The chemical compound of choosing is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination; In this pharmaceutical preparation, except that main active, the Percutaneous absorption enhancer of use is laurocapram (azone Azone) or Mentholum; Absorbing penetration promoter is ethanol or propanol; Both consumptions are 3.0%; Softening agent is glycerol or polyvinyl alcohol, and consumption is 5.0%.Except that main active is prepared by the United States Patent (USP) method, all the other equal commercial goods.
Concrete weight proportion is:
1,1-dimethyl biguanide vanudium complex 100kg, laurocapram or Mentholum 3kg, ethanol or propanol 3kg, glycerol or polyvinyl alcohol 5kg, essence 0.5kg.
Take by weighing all material (solid is ground into the fineness that needs in advance, and is dried to water content≤0.5%) according to dosage, put in the container fully mixing, the substrate mixing that can make with rubber is uniformly coated on a kind of " rubber plaster " formula patch of making on the rib backing material;
Thickness is 250～500 μ m, and every area is 2.5～5.0cm
2, per two are attached to the plastic foil both sides relatively.According to the qualified back of project plastic-aluminum paper tinsel bag packings such as the routine inspection uniformity under the pharmacopeia item, adhesion strength be heat-resisting, cold-resistant, 10 of every bags.
The acupuncture point that suggestion is applied ointment or plaster is 1. shen shus, Qihai, sp 6; 2. cv, water channel, sp 9; Two groups are used alternatingly.Ear acupuncture uses lung, kidney, spleen, endocrine.Directly be affixed on corresponding acupuncture point epidermis, the characteristics and the effect that have acupoint, stimulate the menstrual flow and pass through network.Or the body surface corresponding site at other acupuncture points that need medication or internal organs of applying ointment or plaster of following the doctor's advice, be action time 24 hours.
This product belongs to decentralized in the binding agent substantially, also can make membrane controlled release type, framework controlled release type, small storage storehouse dissolving control release type by prior art.
They are made up of several different levels substantially: outermost is a wrapper, inwardly is medicine storage pond, inwardly is the porous film of one deck again, and the inside is an adhesive attachment layer, and this layer is gone up with a protecting film, faces with before tearing.
After patch sticks, pass through perforated membrane, the speed of control drug release, as long as (patch) storage has a certain amount of medicine in the storehouse, just by zero level process constant release, see through skin again after wherein drug main will discharge by the microporous membrane diffusion and enter the blood capillary clump, and then be diffused into whole body, performance treatment effectiveness.
Patient's the state of an illness and individual variation are different, and suggestion please be followed the doctor's advice as the consumption of the biguanide vanudium complex of the said structure of main active.
The present invention can also be used for the treatment of the purposes of blood pressure lowering preparation, obesity appetite suppressant and hypercholesterolemia, the preparation of high triglyceride adjusting patch except that the medicine biguanide vanudium complex patch preparation that is mainly used in the treatment diabetes.
Embodiment 2
The chemical compound of choosing is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination; In this pharmaceutical preparation, the Percutaneous absorption enhancer that uses except that main active is a laurocapram; Absorbing penetration promoter is ethanol or propylene glycol; Softening agent is glycerol or polyvinyl alcohol.
Concrete weight proportion is:
1,1-dimethyl biguanide vanudium complex 100kg, laurocapram 5kg, ethanol or propylene glycol 2.5kg, glycerol or polyvinyl alcohol 3kg, essence 0.5kg.
Through conventional moulding, system cream, coating, drying, shearing, pack the patch of decentralized in the binding agent; Surplus with embodiment 1.Embodiment 3
Main active is a 1-phenformin vanudium complex, vanadium in the complex and oxygen coordination; In this pharmaceutical preparation, the Percutaneous absorption enhancer that uses except that main active is Borneolum Syntheticum or Oleum Eucalypti; Absorbing penetration promoter is isopropyl alcohol or isobutanol; Softening agent is ethylene pyrrolidone or lanoline.
Concrete weight proportion is: 1-phenformin vanudium complex 100kg, Borneolum Syntheticum or Oleum Eucalypti 7kg, isopropyl alcohol or isobutanol 3.5kg, ethylene pyrrolidone or lanoline 4kg.
Often regulation is equipped with membrane controlled release type or framework controlled release type patch; All the other are with embodiment 1.
Embodiment 4
Main active is 1,1-dibutyl biguanide vanudium complex, vanadium in the complex and oxygen coordination; In this pharmaceutical preparation, except that main active, the Percutaneous absorption enhancer of use is an Oleum Eucalypti; Absorbing penetration promoter is normal propyl alcohol; Softening agent is a lanoline.
Concrete weight proportion is: 1, and 1-two dibutyl biguanide vanudium complex 100kg, Oleum Eucalypti 6kg, normal propyl alcohol 5kg, lanoline 4.5kg, essence 0.35kg.Often regulation is equipped with the membrane controlled release type patch; All the other are with embodiment 1.
Embodiment 5
Main active is 1,1-dipropyl biguanide vanudium complex, vanadium in the complex and sulfur coordination; In this pharmaceutical preparation, except that main active, the Percutaneous absorption enhancer of use is laurocapram and Borneolum Syntheticum; Absorbing penetration promoter is ethanol or propylene glycol; Softening agent is lanoline and polyvinyl alcohol.
Concrete weight proportion is: 1, and 1-dipropyl biguanide vanudium complex 100kg, laurocapram 5kg, Borneolum Syntheticum 3kg, normal propyl alcohol 5kg, ethanol 3kg lanoline 2.5kg, polyvidon 3.5kg.Often regulation is equipped with framework controlled release type patch; All the other are with embodiment 1.
Embodiment 6
Main active is 1,1-dipropyl or diisopropyl biguanide vanudium complex, vanadium in the complex and sulfur coordination; In this pharmaceutical preparation, the Percutaneous absorption enhancer that uses except that main active is laurocapram and Borneolum Syntheticum; Absorbing penetration promoter is ethanol or propylene glycol; Softening agent is lanoline and polyvinyl alcohol.
Concrete weight proportion is: 1, and 1-dipropyl or diisopropyl biguanide vanudium complex 100kg, laurocapram 5kg, Borneolum Syntheticum 3kg, normal propyl alcohol 5kg, ethanol 3kg lanoline 2.5kg, polyvidon 3.5kg.Often regulation is equipped with framework controlled release type patch; All the other are with embodiment 1.
Embodiment 7
Main active is 1,1-diethyl biguanide vanudium complex, vanadium in the complex and nitrogen coordination; In this pharmaceutical preparation, except that main active, the Percutaneous absorption enhancer of use is laurocapram and Mentholum; Absorbing penetration promoter is ethanol; Softening agent is lanoline and polyvinyl alcohol.
Concrete weight proportion is: 1, and 1-diethyl biguanide vanudium complex 100kg, laurocapram 3kg, Mentholum 5kg, ethanol 8kg lanoline 2.5kg, polyvidon 3.5kg.Often regulation is equipped with framework controlled release type patch; All the other are with embodiment 1.
Embodiment 8
Main active is a 1-cycloalkyl biguanide vanudium complex, vanadium in the complex and sulfur coordination, and in this pharmaceutical preparation, except that main active, the Percutaneous absorption enhancer of use is Borneolum Syntheticum or Oleum Eucalypti; Absorbing penetration promoter is isopropyl alcohol or isobutanol; Softening agent is ethylene pyrrolidone or lanoline.
Concrete weight proportion is: 1-cycloalkyl biguanide vanudium complex 100kg, Borneolum Syntheticum or Oleum Eucalypti 8kg, isopropyl alcohol or isobutanol 5.5kg, ethylene pyrrolidone or lanoline 4.5kg.Often regulation is equipped with membrane controlled release type or framework controlled release type patch; Surplus with example 1.
Embodiment 9
Main active is a 1-phenyl biguanide vanudium complex, vanadium in the complex and nitrogen coordination, and in this pharmaceutical preparation, except that main active, the Percutaneous absorption enhancer of use is an Oleum Eucalypti; Absorbing penetration promoter is normal propyl alcohol; Softening agent is a lanoline.
Concrete weight proportion is: 1-phenyl biguanide vanudium complex 100kg, Oleum Eucalypti 6kg, normal propyl alcohol 7kg, lanoline 4.5kg.Often regulation is equipped with the membrane controlled release type patch; All the other are with embodiment 1.
Embodiment 10
Main active is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
1,1-dimethyl biguanide vanudium complex 100kg, laurocapram or Mentholum 3kg, ethanol or propanol 3kg, glycerol or polyvinyl alcohol 5kg.Make " rubber plaster " formula patch according to routine; All the other are with embodiment 1.
Embodiment 11
Main active is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination; 1,1-dimethyl biguanide vanudium complex 100kg, laurocapram 7kg, ethanol 5kg, glycerol 3kg, polyvinyl alcohol 5kg, essence 0.5kg.
According to the conventional patch that makes decentralized in the binding agent; All the other are with embodiment 1.
Embodiment 12
Main active is a 1-phenformin vanudium complex, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1-phenformin vanudium complex 100kg, laurocapram 3kg, Oleum Eucalypti 7kg, isopropyl alcohol 3.5kg, isobutanol 3.5kg, ethylene pyrrolidone 4kg, lanoline 4kg, essence 0.4kg.Often regulation is equipped with membrane controlled release type or framework controlled release type patch; All the other are with embodiment 1.
Embodiment 13
Main active is 1,1-dibutyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1, and 1-dibutyl biguanide vanudium complex 100kg, Oleum Eucalypti 8kg, ethanol 4kg, normal propyl alcohol 5kg, lanoline 4.5kg.
Often regulation is equipped with the membrane controlled release type patch; All the other are with embodiment 1.
Embodiment 14
Main active is 1,1-dipropyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1, and 1-dipropyl biguanide vanudium complex 100kg, laurocapram 5kg, Borneolum Syntheticum 3kg, normal propyl alcohol 5kg, ethanol 3kg lanoline 2.5kg, polyvidon 3.5kg.Often regulation is equipped with framework controlled release type patch; All the other are with embodiment 1.
Embodiment 15
Main active is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1, and 1-dimethyl biguanide vanudium complex 100kg, laurocapram 5kg, Borneolum Syntheticum 3kg, normal propyl alcohol 3kg, ethanol 5kg lanoline 3.5kg, polyvidon 2.5kg.Often regulation is equipped with framework controlled release type patch; All the other are with embodiment 1.
Embodiment 16
Main active is 1,1-27 basic biguanide vanudium complexs, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1, and 1-diethyl biguanide vanudium complex 100kg, laurocapram 3kg, Mentholum 5kg, ethanol 8kg lanoline 2.5kg, polyvidon 3.5kg.Often regulation is equipped with framework controlled release type patch; All the other are with embodiment 1.
Embodiment 17
Main active is a 1-cycloalkyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1-cycloalkyl biguanide vanudium complex 100kg, Borneolum Syntheticum 2kg, or Oleum Eucalypti 8kg, isopropyl alcohol 2.5kg, isobutanol 5.5kg, ethylene pyrrolidone 2.5kg lanoline 4.5kg.Often regulation is equipped with membrane controlled release type or framework controlled release type patch; All the other are with embodiment 1.
Embodiment 18
Main active is a 1-phenyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
Concrete weight proportion is: 1-phenyl biguanide vanudium complex 100kg, Oleum Eucalypti 6kg, normal propyl alcohol 7kg, lanoline 4.5kg.Often regulation is equipped with the membrane controlled release type patch; All the other are with embodiment 1.
Embodiment 19
Main active is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
1,1-dimethyl biguanide vanudium complex 100kg, laurocapram or Mentholum 3kg, ethanol or propanol 3kg, glycerol or polyvinyl alcohol 5kg.
Make small storage storehouse dissolving control release type patch according to routine; All the other are with embodiment 1.
Embodiment 20
Main active is 1,1-dimethyl biguanide vanudium complex, vanadium in the complex and oxygen coordination;
1,1-dimethyl biguanide vanudium complex 100kg, laurocapram 7kg, ethanol 5kg, glycerol 3kg, polyvinyl alcohol 5kg, essence 0.5kg.
According to the conventional patch that makes decentralized in the binding agent; All the other are with embodiment 1.
Claims (9)
1. patch for the treatment of diabetes medicament biguanide vanudium complex is characterized in that:
(1) contain in this medicine patch structure as shown in the formula chemical compound as main active
R wherein
1And R
2Be selected from H, methyl, ethyl, propyl group, isopropyl, butyl, cycloalkyl, phenyl or phenethyl respectively;
Activated complex comprises the biguanide chelating agen, and the biguanide chelating agen of preferred 1 replacement can form a hexa-atomic unsaturated vanadium containing ring by the chelating vanadium; Vanadium in the complex and oxygen, sulfur or nitrogen coordination are preferably with the oxygen coordination;
(2) in this medicine patch, except that containing the main active for the treatment of effective dose, also contain Percutaneous absorption enhancer, transdermal absorption penetration promoter and softening agent.
2. according to the patch of the described treatment diabetes medicament of claim 1 biguanide vanudium complex, it is characterized in that wherein said main active is 1,1-dimethyl biguanide vanudium complex.
3. according to the patch of the described treatment diabetes medicament of claim 1 biguanide vanudium complex, it is characterized in that wherein said main active is a 1-phenformin vanudium complex.
4. according to the patch of the described treatment diabetes medicament of claim 1 biguanide vanudium complex, it is characterized in that wherein said main active is a 1-butyl biguanide vanudium complex.
5. according to the patch of claim 1,2,3 or 4 described treatment diabetes medicament biguanide vanudium complexs, it is characterized in that wherein said vanadium is to exist with V (IV) or V (V) form.
6. according to the patch of claim 1,2,3 or 4 described treatment diabetes medicament biguanide vanudium complexs, it is characterized in that described Percutaneous absorption enhancer is laurocapram, Mentholum, Borneolum Syntheticum or Oleum Eucalypti, the mixture of wherein one or more.
7. according to the patch of claim 1,2,3 or 4 described treatment diabetes medicament biguanide vanudium complexs, it is characterized in that described transdermal absorption penetration promoter is ethanol, propanol, butanols or propylene glycol, the mixture of wherein one or more.
8. according to the patch of claim 1,2,3 or 4 described treatment diabetes medicament biguanide vanudium complexs, it is characterized in that described softening agent is glycerol, polyvinyl alcohol, polyvidon or lanoline, the mixture of wherein one or more.
9. according to the application of the patch of claim 1,2,3 or 4 described treatment diabetes medicament biguanide vanudium complexs, it is characterized in that except that the medicinal usage of preparation treatment diabetes, can also be used to prepare the purposes of blood pressure lowering preparation, obesity appetite suppressant and hypercholesterolemia, high triglyceride adjusting preparation.
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| CN101953846A (en) * | 2010-06-24 | 2011-01-26 | 攀枝花兴辰钒钛有限公司 | Application of medicinal composition to preparing medicament for treating diabetes |
| CN101972273A (en) * | 2010-10-29 | 2011-02-16 | 攀枝花兴辰钒钛有限公司 | Application of medicine in preparing medicines for treating diabetes mellitus |
| WO2011160444A1 (en) * | 2010-06-24 | 2011-12-29 | 攀枝花东方微元科技有限公司 | Pharmaceutical composition comprising vanadium and its use |
| WO2012131689A1 (en) | 2011-03-25 | 2012-10-04 | Chaudhuri Mihir K | Insulin mimetic active comprising oxodiperoxo vanadates and a pharamaceutical composition obtained thereof |
| CN115282162A (en) * | 2022-08-22 | 2022-11-04 | 南通大学 | Transdermal-release nano application for treating diabetes and preparation method thereof |
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| CN101953846A (en) * | 2010-06-24 | 2011-01-26 | 攀枝花兴辰钒钛有限公司 | Application of medicinal composition to preparing medicament for treating diabetes |
| CN101978965A (en) * | 2010-06-24 | 2011-02-23 | 攀枝花兴辰钒钛有限公司 | Use of medicine in treating diabetes |
| CN101953846B (en) * | 2010-06-24 | 2011-12-28 | 攀枝花兴辰钒钛有限公司 | Application of medicinal composition to preparing medicament for treating diabetes |
| CN101978965B (en) * | 2010-06-24 | 2011-12-28 | 攀枝花兴辰钒钛有限公司 | Use of medicine in treating diabetes |
| WO2011160444A1 (en) * | 2010-06-24 | 2011-12-29 | 攀枝花东方微元科技有限公司 | Pharmaceutical composition comprising vanadium and its use |
| WO2011160443A1 (en) * | 2010-06-24 | 2011-12-29 | 攀枝花东方微元科技有限公司 | Pharmaceutical composition comprising vanadium and its use |
| CN102302510A (en) * | 2010-06-24 | 2012-01-04 | 攀枝花兴辰钒钛有限公司 | Medicinal composition and application thereof |
| CN101972273A (en) * | 2010-10-29 | 2011-02-16 | 攀枝花兴辰钒钛有限公司 | Application of medicine in preparing medicines for treating diabetes mellitus |
| CN101972273B (en) * | 2010-10-29 | 2011-12-21 | 攀枝花兴辰钒钛有限公司 | Application of medicine in preparing medicines for treating diabetes mellitus |
| WO2012131689A1 (en) | 2011-03-25 | 2012-10-04 | Chaudhuri Mihir K | Insulin mimetic active comprising oxodiperoxo vanadates and a pharamaceutical composition obtained thereof |
| CN115282162A (en) * | 2022-08-22 | 2022-11-04 | 南通大学 | Transdermal-release nano application for treating diabetes and preparation method thereof |
| CN115282162B (en) * | 2022-08-22 | 2024-02-20 | 南通大学 | Transdermal release nano-application for treating diabetes mellitus and preparation method thereof |
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