CN101152198A - Nasal cavity administration preparation for treating diabetes - Google Patents
Nasal cavity administration preparation for treating diabetes Download PDFInfo
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- CN101152198A CN101152198A CNA2006100487003A CN200610048700A CN101152198A CN 101152198 A CN101152198 A CN 101152198A CN A2006100487003 A CNA2006100487003 A CN A2006100487003A CN 200610048700 A CN200610048700 A CN 200610048700A CN 101152198 A CN101152198 A CN 101152198A
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- ginsenoside
- qualified qualified
- preparation
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Abstract
The invention relates to a medicament for treating diabetes by nasal administration. Wherein each 1ml or 1g contains ginsenoside monomer Re and/or Rg110 mg-500 mg, and various preparation formulations for nasal administration are prepared by adopting different preparation processes. The preparation of the invention has the advantages of definite drug effect for treating diabetes, convenient use, rapid effect, small administration volume and small toxicity to nasal cilia.
Description
Technical field
The present invention relates to field of pharmaceutical technology, specifically a kind of nasal cavity administrated preparation that contains the treatment diabetes of ginsenoside monomer.
Background technology
Diabetes are increasing to the influence of human health, serious threat people's life, and its mortality rate is only second to cardiovascular and cerebrovascular disease, cancer, occupies the 3rd.Diabetes are a kind of commonly encountered diseases, and along with growth in the living standard, the sickness rate of diabetes increases year by year.The prevalence of developed country's diabetes is up to 5%～10%, and the prevalence of China has reached 3%.At present China's diabetics reaches 4,500 ten thousand, and annually strides into the medium prevalence of diabetes country ranks also with 80 to 1,000,000 speed increment from the low prevalence country of diabetes, is the maximum country of onset diabetes number.Diabetes have become one of main public health problem in the whole world, and the newtype drug of development treatment diabetes has become very urgent thing.
Just find that panax species has certain therapeutical effect to metabolic diseases such as diabetes in the tradition Clinical Application, present Radix Notoginseng total arasaponins preparation finds also that in pharmacology and clinical research diabetes and complication thereof are had certain curative effect, research confirms that also some ginsenoside monomer also has effects such as blood sugar lowering, and the effect of drug administration by injection obviously is better than oral administration, sometimes even the invalid situation of oral administration occurs.But for this chronic disease of diabetes, need long term administration, and diabetes patient's blood vessel is vulnerable to injury, stays cicatrix, therefore, should not adopt the mode administration of long term injections.
The ginsenoside Re has the inhibition nervus centralis, promotes DNA, RNA synthetic, pharmacological actions such as blood sugar lowering.Be used for the treatment of arrhythmia, myocardial ischemia reperfusion injury etc. clinically.Just reported ginsenoside Re's hypoglycemic activity (external medicine-2003 the 18th the 1st phases of volume of plant amedica fascicle) as far back as Attele AS in 2002.Patent " Herba Herminii triol saponins extract and extraction, process for purification and medical usage thereof " (CN 1537863A) has also been illustrated ginsenoside Re's hypoglycemic activity.
The ginsenoside Rg
1The energy stimulating central nervous system prevents sexual hypofunction, and memory reinforcing sets up, and promotes DNA, RNA synthetic, anti-platelet aggregation, blood sugar lowering etc.Ginsenoside Rg clinically
1(seven give birth to power sheet) are used for the treatment of due to the blood stasis due to qi deficiency dizzy weak, forgetful.Domestic as far back as nineteen eighty-two with regard to useful ginsenoside Rg
1Research report (Acta Pharmaceutica Sinica 1982 to the influence of mice fasting glucose; 17 (3): 23).Afterwards, Du Yuanchong has also reported with Radix Notoginseng total Saponin of floss root and arasaponin Cl (ginsenoside Rg
1) to the influence (Yunnan Pharmaceutical Institute, 1983) of mouse blood sugar.Illustrated the ginsenoside Rg
1Hypoglycemic activity.
Ginsenoside Re's biological half-life short and oral after easily be hydrolyzed, and this chronic disease of diabetes, need long term administration, the oral administration bioavailability is low.The ginsenoside Rg
1The oral formulations bioavailability is lower, only is 1.9%～20%.For this chronic disease of diabetes, need long term administration, and diabetes patient's blood vessel be vulnerable to the injury, stay cicatrix, therefore, should not adopt the mode administration of long term injections.And the nasal-cavity administration approach has topical performance whole body drug effect, the bioavailability height, and advantage such as easy to use, patient's compliance is good, and is quick-acting therefore in order to overcome the treatment shortcoming of injection and oral formulations, adopts the nasal-cavity administration approach to receive publicity.
Summary of the invention
The purpose of this invention is to provide a kind of treat diabetes contain ginsenoside Re and/or Rg
1Nasal cavity administrated preparation.Its drug effect is definite, and rapidly, the administration volume is little, and is little to nasal ciliary toxicity.
Ginsenoside Re who the present invention relates to and/or Rg
1Nasal cavity administrated preparation adopts the pharmaceutics technology, makes ginsenoside Re and/or Rg in the preparation
1Every 1ml or every 1g contain ginsenoside Re and/or Rg
110mg～500mg, optimum is 20mg～300mg.Ginsenoside Re who the present invention relates to and/or Rg
1Nasal cavity administrated preparation has the advantage that reduces administration volume and administration number of times.
People's bronchia mucosal surface area reaches 150 square centimeters, and the top layer epithelium has a large amount of nose ciliums, and it is extremely important to keep normal physiological function for human body.It not only can remove foreign body in nose, prevents that airborne granule from entering pulmonary; And be the important immunologic barrier of body, it can prevent that extrinsic protein, virus and antibacterial are inhaled in the body.Nasal cavity administrated preparation must be less for nose cilium zest.Radix Ginseng saponin Re of the present invention and/or Rg
1Nasal cavity administrated preparation has the advantage little to nasal ciliary toxicity.
Ginsenoside Re of the present invention and/or Rg
1Ginsenoside Re in the nasal cavity administrated preparation and/or Rg
1Derive from crude drug Radix Notoginseng, Radix Ginseng, Radix Panacis Quinquefolii, semisynthetic, can buy from the market, purity requirement is 85%～99.99%.
Nasal cavity administrated preparation of the present invention can be nasal drop, aerosol, spray, gel, ointment, Emulsion, liposome, membrane, powder agent (comprising powder agent, microsphere nasal powder, solid dispersion nasal powder, cyclodextrin clathrate nasal powder etc.) or microparticle formulation.
Nasal cavity administrated preparation of the present invention also can contain the ginsenoside Re and/or the Rg of therapeutic dose
1And one or more excipient, comprise penetration enhancer, diluent, solubilizing agent, emulsifying agent, wetting agent, dispersant, aqueous or oleaginous base, thickening agent, stabilizing agent, antiseptic, aromatic and pH buffer agent etc.
In addition, ginsenoside Re in the preparation and/or Rg
1Can add in a variety of forms, comprise micronization, solid dispersion, clathrate, microsphere, liposome and nanoparticle etc.
Nasal cavity administrated preparation of the present invention can with macromolecular compound have: cellulose derivative such as sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose etc. and xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone (PVP), polylactide Acetic acid, hydroxy-, bimol. cyclic ester (PLGA), carbopol, polyvidone, alginate, arabic gum, tragacanth, chitosan are by its adjusting to preparation toughness, but the time of contact of prolong drug and nasal mucosa, improve bioavailability.Wherein antiseptic should be harmless in the Mlc scope, nonirritant, no off-odor, do not influence the physicochemical property of preparation.For example p-Hydroxybenzoate, benzoic acid and salt thereof, sorbic acid, chlorobutanol, benzyl alcohol, ethyl hydroxybenzoate, bromo geramine, phenethanol, chlorhexidine acetate, thimerosal and quaternary ammonium compound cationoid surfactant etc.
The stabilizing agent that can add in the preparation of the present invention has antioxidant such as sodium pyrosulfite, sodium sulfite, sodium sulfite, sodium thiosulfate, ascorbic acid, thiourea, cysteine, tocopherol and lecithin etc.The preferred of aforementioned stable agent consumption is 0.01%～5% (w/v) of preparation.Other intercalating agent that can add has ethylenediaminetetraacetic acid, disodiumedetate, citric acid, tartaric acid etc.The preferred amounts of above-mentioned intercalating agent is 0.005%～0.05% (w/v).
Beta-schardinger dextrin-and derivant thereof such as beta-schardinger dextrin-, HP-, DM-can with ginsenoside Re and/or Rg
1Form clathrate, increase its stability; Simultaneously, help preparing various solid preparations.
Wetting agent can be one or more in sorbitol, glycerol, propylene glycol, mineral oil, the vegetable oil among the present invention.
Solubilizing agent can be poly yamanashi esters (Tweens) among the present invention, fatty acid esters of sorbitan class (spans), the polyethylene glycol alkyl ether class is (as brejs, Polyethylene Glycol hexadecanol ether), Polyethylene Glycol and alkyl esters thereof (Myrij class), diethylene glycol alkyl ether such as TC, diethylene glycol dimethyl ether, diethylene glycol alkyl vinegar class such as the acid of diethylene glycol distearyl are cruel, the diethylene glycol dilaurate, triethylene glycol alkyl esters such as triethylene glycol dilaurate, in triethylene glycol list cinnamate nonionic surfactant and anionic surfactant such as the sodium laurylsulfate one or more.
The emulsifying agent of this nasal cavity administrated preparation can be Tweens, spans, polyxyethylated ester such as polyoxyethylene 400 monolaurates, polyoxyethylene 400 monostearates, polyoxyethylene 400 monoleates, polyoxyethylene alkyl ether such as peregal 0, polyoxyethylene nonylphenol ether, poloxalkol class (Poloxamer), 16-18 alcohol ether-6,16-18 alcohol ether-25 non-ionic surface active agent, one or more in sodium laurylsulfate, soap kind anion surfactant and the natural gum.
The penetration enhancer of this nasal cavity administrated preparation has polyoxyethylene-9-Laurel ether, sodium laurylsulfate; chlolic acid derivatives; taurine, hyaluronic acid; beta-schardinger dextrin-, hydroxypropyl-beta-schardinger dextrin-, DM-, glycyrrhizic acid dipotassium, azone, EDTA, Borneolum Syntheticum, chitosan, cyclic peptide class such as surfactant such as tween, span, polyoxyethylene laurel ether and bacitracin.Its consumption is about 0.005%～10%, and preferred amounts is 0.01%～5%.Above-mentioned substance has solubilising, emulsification simultaneously.
Aromatic can be one or more in cinnamic aldehyde, vanillin, Oleum menthae, the edible essence.Edible essence can be Fructus Citri tangerinae, Fructus Ananadis comosi, Fructus Musae, Fructus Myricae rubrae, Fructus Persicae, Fructus Citri Limoniae, Rhizoma et radix valerianae.
Pharmacological toxicology research of the present invention:
Observe its blood sugar decreasing effect and mucosa cilium toxicity by animal experiment.
1. the embodiment of the invention 1,2 and 3 products cause the influence of hyperglycemia to injectable dextrose monohydrate
24 rabbit fasting in afternoon on the previous day are divided into 6 groups, 4 every group.The experimental group nasal cavity gives above-mentioned preparation 0.2ml/ and only (is equivalent to the ginsenoside Rg
12mg), each nostril 0.1ml; Rg
1Oral matched group: oral administration gavage administration Rg
150mg/ only; The oral matched group of Re: oral administration gavage administration Re 50mg/ only; 4 of normal saline groups, nasal cavity only give normal saline 0.2ml/, each nostril 0.11ml, and after this 2 hours pneumoretroperitoneum injectable dextrose monohydrates of administration, 3～8g/kg got blood at 0.5～5 hour by auricular vein, measured blood glucose with the ortho-aminotoluene method.The result shows, the ginsenoside Rg
1Nasal cavity administrated preparation have significantly with the blood glucose effect.
Table 1 product causes the influence of hyperglycemia to injectable dextrose monohydrate
| Group | Normal fasting glucose (mg%) | Blood glucose mg% behind the lumbar injection glucose | ||||
| 1hr | 2hr | 3hr | 4hr | 5hr | ||
| Embodiment 1 | 118 | 185.1 | 162.3 | 140.9 | 94.8 | 123.7 |
| Embodiment 2 | 116 | 180.41 | 158.1 | 135.6 | 114.2 | 123.3 |
| Embodiment 3 | 120 | 192.7 | 168.5 | 143.4 | 116.3 | 112.5 |
| Rg1 is oral | 119 | 198.2 | 188.5 | 180.9 | 154.8 | 133.7 |
| Re is oral | 122 | 193.1 | 172.3 | 160.9 | 149.2 | 138.2 |
| The normal saline group | 117 | 195.6 | 192.1 | 188.4 | 172.5 | 82.6 |
2. product is to the influence of alloxan diabetes man rabbit blood glucose
8 of alloxan diabetes rabbit are divided into two groups.First group 4, nasal cavity gives above-mentioned preparation 0.2ml/ and only (is equivalent to the ginsenoside Rg
12mg), each nostril 0.1ml; Second group 4, nasal cavity only gives normal saline 0.2ml/, each nostril 0.11ml, and administration was got blood by auricular vein after 1 hour, sent out mensuration blood glucose with ortho-aminotoluene.The result shows, the ginsenoside Rg
1Nasal cavity administrated preparation have significantly with the blood glucose effect.
Table 2 test products is to the influence of alloxan diabetes man rabbit blood glucose
| Group | Alloxan diabetes man rabbit blood glucose (mg%) | Nasal cavity is given the blood glucose mg% behind the normal saline behind the said preparation | ||||
| 1hr | 2hr | 3hr | 4hr | 5hr | ||
| Embodiment 1 | 218 | 204.2 | 185.6 | 164.9 | 154.8 | 123.7 |
| Embodiment 2 | 225 | 203.7 | 178.2 | 159.7 | 148.5 | 128.2 |
| Embodiment 3 | 236 | 205.3 | 191.1 | 154.6 | 136.2 | 120.3 |
| Rg 1Oral | 222 | 216.5 | 208.2 | 193.5 | 175.3 | 154.6 |
| Re is oral | 219 | 209.2 | 180.5 | 164.3 | 159.6 | 145.9 |
| The normal saline group | 232 | 228.6 | 222.3 | 216.8 | 212.5 | 208.5 |
3. test products is to the influence of Bufo siccus maxillary mucosa cilium
For above-mentioned preparation, adopt the Bufo siccus maxillary model evaluation cilium toxicity that exsomatizes.The Bufo siccus maxillary mucosa cilium persistent movement time that it has been generally acknowledged that test group is more than 60% of physiology saline control group, and test preparation cilium toxicity is less.As a result, the average persistent movement time of Bufo siccus maxillary mucosa cilium (three tests) is respectively 85%, 84%, 83% of normal saline matched group behind the said preparation administration 30min.The result confirms that preparation of the present invention is little to nasal ciliary toxicity.
Table 3 test products is to the influence of Bufo siccus maxillary mucosa cilium
| Experiment number | The normal saline persistent movement time (min) | The nasal cavity preparation persistent movement time (min) | ％ | |
| Embodiment 1 | 1 | 1563 | 1297 | 83％ |
| Embodiment 1 | 2 | 2540 | 2235 | 88％ |
| Embodiment 1 | 3 | 3758 | 3157 | 84％ |
| On average | 85％ | |||
| Embodiment 2 | 1 | 1645 | 1383 | 84％ |
| Embodiment 2 | 2 | 2621 | 2232 | 85％ |
| Embodiment 2 | 3 | 3826 | 3175 | 83％ |
| On average | 84％ | |||
| Embodiment 3 | 1 | 1596 | 1308 | 82％ |
| Embodiment 3 | 2 | 2532 | 2177 | 86％ |
| Embodiment 3 | 3 | 3845 | 3230 | 84％ |
| On average | 83％ | |||
Above-mentioned preparation room temperature was placed 2 years, detected its content through HPLC, did not change basically, and all the other every indexs are all up to specification.
The result of study of product stability:
Above-mentioned prescription preparation is carried out long-time stability investigate, liquid preparation detects TLC discriminating, clarity, microbial limit, loading amount, content (HPLC detection) item; Solid preparation detects TLC discriminating, microbial limit, loss on drying, loading amount, content (HPLC detection) item; All the other every regulations that should meet nasal cavity administrated preparation are to know the result who has carried out 2 years long-term study on the stability to above-mentioned below:
0 month long-time stability of table 4 are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
Table 5 long-time stability in January are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
Table 6 long-time stability in March are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
Table 7 long-time stability in June are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
Table 8 JIUYUE long-time stability are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
Table 9 December long-time stability are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
18 months long-time stability of table 10 are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
24 months long-time stability of table 11 are investigated the result
| Prescription | TLC differentiates | Clarity | Microbial limit | Loss on drying | Loading amount | Content |
| Embodiment 1 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 2 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 3 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 4 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 5 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 6 | Positive | Qualified | Qualified | - | Qualified | Qualified |
| Embodiment 7 | Positive | - | Qualified | Qualified | Qualified | Qualified |
| Embodiment 8 | Positive | - | Qualified | Qualified | Qualified | Qualified |
The specific embodiment
Embodiment 1: by following set of dispense ratio preparation solution
The ginsenoside Rg
11.0g
Tween 80 2.0ml
Propylene glycol 30ml
Benzyl alcohol 1.0ml
Distilled water adds to 100ml
With the ginsenoside Rg
1Add suitable quantity of water, add the dissolving of Tween 80, propylene glycol again after, add benzyl alcohol, adding distil water adds to 100ml promptly again.Above-mentioned preparation can be used for collunarium or nasal spray administration.
Embodiment 2: by following set of dispense ratio preparation Emulsion
Ginsenoside Re 3.0g
Oleum Ricini 25ml
Arabic gum 1.25g
Tragacanth 1.25g
Sodium deoxycholate 1g
Distilled water is added to 100ml
The ginsenoside Re is added suitable quantity of water dissolving and Oleum Ricini be added in the mortar and grind well, add arabic gum, tragacanth, sodium deoxycholate and about 25ml distilled water, colostrum is made in grinding rapidly, adds distilled water again to 100ml, makes white Emulsion.
Embodiment 3: by following set of dispense ratio preparation gel
Ginsenoside Re 1.5g Rg
15.8g
Beta-schardinger dextrin-4g
Carbopol 934PN 0.5g
Borneolum Syntheticum 0.9g
Distilled water is an amount of
Make gel 100g
Beta-schardinger dextrin-is added in the 50ml distilled water, be heated to dissolving fully, pour the ginsenoside Rg into
1With Re, Borneolum Syntheticum, ultrasound wave enclose 2h adds carbopol 934PN, and magnetic agitation 24h transfers pH to 6～7 one-tenth gels with 1mol/LNaoH, and adding distil water gets white gels to 100g.
Embodiment 4: by following set of dispense ratio preparation powder agent
Ginsenoside Re 3g
The ginsenoside Rg
12g
Beta-schardinger dextrin-4g
Distilled water 25ml
Azone 0.9g
Lactose is an amount of
Beta-schardinger dextrin-is added in the 50ml distilled water, be heated to dissolving fully, pour the ginsenoside Rg into
1, azone, ultrasound wave enclose 2h filters; The solids lyophilization adds lactose to 25g, and mixing is crossed 120 mesh sieves, sucks for nasal cavity and uses.
Embodiment 5: by following set of dispense ratio preparation microsphere nasal powder
Ginsenoside Re 3.75g
The ginsenoside Rg
13.75g
Polylactide Acetic acid, hydroxy-, bimol. cyclic ester (PLGA) 17.4g
Polyvinyl alcohol (PVA) 0.1g
Bromo geramine 0.01g
Method for making: get PLGA, adding methylene chloride is dissolved to 100ml, and other gets ginsenoside Re and ginsenoside Rg
1And bromo geramine, adding distil water 20ml stirs and makes dissolving, carries out breast under the 22000rpm condition and spares, and makes to form the W/0 colostrum; Other gets PVA, adds water 500ml and makes dissolving, and colostrum is poured in the PVA solution, stirs to form the W/O/W emulsion; Emulsion is moved into 500ml contains in the aqueous solution of 0.5%PVA, place on the mechanical agitator under the 500rpm rotating speed stirred for several hour, centrifugal, collect thus obtained microsphere, with distilled water wash repeatedly after, centrifugal again collection, lyophilization promptly gets ginsenoside Re and ginsenoside Rg
1/ PLGA microsphere nasal powder 25g, directly administration or add aqueous dispersion after spray delivery.
Embodiment 6: produce the nose hydrojet that contains adhesive agent CarboPol
Ginsenoside Re 50g
Card pool nurse (Carbopol) 0.2g
Ethyl hydroxybenzoate 0.05g
Distilled water adds to 100ml
Method for making: will block the immersion of pool nurse adding distil water and make swelling, and add ginsenoside Re, ethyl hydroxybenzoate successively, and stir and make whole dissolvings, adding distil water stirs evenly to 100ml, promptly gets the nose hydrojet of adhesive agent Carbopol.
Embodiment 7: make the solid dispersion nasal powder by following prescription
The ginsenoside Rg
112.5g
Polyethylene adjoins coughs up alkane alkane ketone (PVP) 7.4g
Bromo geramine 0.1g
Ethanol 100ml
Method for making: get PVP and ginsenoside Rg
1, adding 95% dissolve with ethanol, 45-70 ℃ of scope internal rotation evaporation removes and desolvates, and the evaporate to dryness thing is crossed 120 mesh sieves, adds bromo geramine, mixing, vacuum drying promptly gets the ginsenoside Rg
1/ PVP solid dispersion 25g.This nasal powder can be directly by administration or add aqueous dispersion after spray delivery.
Embodiment 8: make the cyclodextrin clathrate nasal powder by following prescription
Ginsenoside Re 6.25g
The ginsenoside Rg
16.25g
Hydroxypropyl (the 12.4g of Hp-β-CD)
Bromo geramine 0.1g
95% ethanol 100ml
Method for making: get HP-β-CD and ginsenoside Re, ginsenoside Rg
1, adding 95% dissolve with ethanol, 45-70 ℃ of scope internal rotation evaporation removes and desolvates, and the evaporate to dryness thing is crossed 120 mesh sieves, adds bromo geramine, mixing, vacuum drying promptly gets ginsenoside Re, ginsenoside Rg
1/ HP-beta-CD inclusion 25g, directly administration or add aqueous dispersion after spray delivery.
Ginsenoside Re in the nasal cavity administrated preparation among the above embodiment and Rg
1Purity be 85%～99.99%.
The present invention describes by above description and embodiment, more than is described as nonrestrictively, does not limit claim scope of the present invention.
Claims (4)
1. a nasal cavity administrated preparation for the treatment of diabetes is characterized in that ginsenoside monomer Re and/or Rg that every 1ml or every 1g contain
1Be 10mg～500mg.
2. the nasal cavity administrated preparation of treatment diabetes according to claim 1 is characterized in that ginsenoside Re and Rg in the described nasal cavity administrated preparation
1Purity be 85%～99.99%.
3. the nasal cavity administrated preparation of treatment diabetes according to claim 1 is characterized in that described nasal cavity administrated preparation is spray, nasal drop, gel, Emulsion, nose hydrojet, nasal powder.
4. the nasal cavity administrated preparation of the described treatment diabetes of claim 1 is characterized in that it is the treatment that is used for diabetes or diabetic complication.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100487003A CN101152198A (en) | 2006-09-29 | 2006-09-29 | Nasal cavity administration preparation for treating diabetes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100487003A CN101152198A (en) | 2006-09-29 | 2006-09-29 | Nasal cavity administration preparation for treating diabetes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101152198A true CN101152198A (en) | 2008-04-02 |
Family
ID=39254217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006100487003A Pending CN101152198A (en) | 2006-09-29 | 2006-09-29 | Nasal cavity administration preparation for treating diabetes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101152198A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022100737A1 (en) * | 2020-11-16 | 2022-05-19 | 江苏先声药业有限公司 | Pharmaceutical composition for nasal administration of glyburide and preparation method therefor |
| CN114588122A (en) * | 2022-03-29 | 2022-06-07 | 中国人民解放军军事科学院军事医学研究院 | Volatile solid preparation and preparation method and application thereof |
-
2006
- 2006-09-29 CN CNA2006100487003A patent/CN101152198A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022100737A1 (en) * | 2020-11-16 | 2022-05-19 | 江苏先声药业有限公司 | Pharmaceutical composition for nasal administration of glyburide and preparation method therefor |
| CN114588122A (en) * | 2022-03-29 | 2022-06-07 | 中国人民解放军军事科学院军事医学研究院 | Volatile solid preparation and preparation method and application thereof |
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