CN1235846A - Medicine preparation administrated through nasal mucosa - Google Patents
Medicine preparation administrated through nasal mucosa Download PDFInfo
- Publication number
- CN1235846A CN1235846A CN 98108852 CN98108852A CN1235846A CN 1235846 A CN1235846 A CN 1235846A CN 98108852 CN98108852 CN 98108852 CN 98108852 A CN98108852 A CN 98108852A CN 1235846 A CN1235846 A CN 1235846A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical preparation
- alkali metal
- metal salt
- insulin
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 210000002850 nasal mucosa Anatomy 0.000 title claims description 28
- 229940079593 drug Drugs 0.000 title description 5
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 37
- -1 alkali metal salt Chemical class 0.000 claims abstract description 34
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 31
- 229920001184 polypeptide Polymers 0.000 claims abstract description 26
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 26
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 26
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 18
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- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960003639 laurocapram Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The medicine preparation dosing through nose macose includes polypeptide compound as the active components; taurine or its alkali metal salt or C1-6 alkyl ester, hyaluronic acid or its alkali metal salt, or their mixture as absorption promoter; and/or other additive and excipient vehicle suitable for use in medicine.
Description
The present invention relates to the pharmaceutical preparation by nasal mucosa medicine administration, more specifically say, what the present invention relates to is pharmaceutical preparation by nasal mucosa medicine administration, and described pharmaceutical preparation comprises the polypeptide compounds as active ingredient, is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or other is suitable for medicinal additive or excipient.
Polypeptide compounds easily is difficult in patient's body to produce due drug effect by metabolism owing to the degraded that is subject to the intestines and stomach enzyme with in liver, and therefore, polypeptide drug is normally with the injection form administration, as subcutaneous, and intramuscular or vein etc.But use polypeptide drug also to bring inconvenience with injection form for a long time to the patient, as needs to hospital go the injection, injecting apparatus will be sterilized, by cause painful of injection with stimulate, and the tissue injury that may cause because of long term injections and the danger of downright bad and potential other disease of infection.Therefore in recent years polypeptide compounds pass through mucosa, cause that as research people pay close attention to greatly by nasal-cavity administration.Chinese patent application numbers 88106763.6, the invention exercise question has disclosed the prescription by mucosa delivery for " prescription by mucosa delivery and preparation method thereof ", wherein used absorption enhancer is sugared or derivatives thereof in this prescription, as be selected from the monosaccharide of D-erythrose, D-ribose, D-ribulose, D-xylose, D-lyxose, L-arabinose, D-mannose, L-sorbose or D-sedoheptulose, be selected from alpha-cyclodextrin, the oligosaccharide of beta-schardinger dextrin-, gamma-cyclodextrin and branched cyclodextrin; Chinese patent application number: 95119260.4 patent of invention has disclosed the promoter of polypeptide medicine mucosa absorbent type, wherein said promoter comprises: laurocapram, saponin, glycyrrhizic acid, Radix Glycyrrhizae acid esters, glycyrrhetate, glycyrrhetinic acid and sodium salt, the acid of dihydroxy Cladrastis kentukea Rudd and derivant thereof, carboxylic acid esters, and the unique example that provides of this patent is a sublingual lozenge.Further say, go back the polypeptide drug preparation listing of neither one by nasal mucosa medicine administration at present, therefore, the polypeptide compounds of exploitation by nasal mucosa medicine administration is still very urgent and needs.
The purpose of this invention is to provide the pharmaceutical preparation that contains polypeptide compounds by nasal mucosa medicine administration.
The inventor has now found that to have and essentially identical pharmaceutically active of drug administration by injection and the non-irritating pharmaceutical preparation that contains polypeptide compounds through nasal mucosa medicine administration through extensively and profoundly research.Say that more specifically the present invention comprises through the pharmaceutical preparation of nasal mucosa medicine administration and polypeptide compounds as active ingredient is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or suitable other medical additive or excipient the present invention is based on above-mentioned discovery and are accomplished.
First aspect present invention relates to is the pharmaceutical preparation that contains polypeptide compounds through nasal mucosa medicine administration, and this pharmaceutical preparation comprises the polypeptide compounds as active ingredient, is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or other is suitable for medicinal excipient or additive.
What second aspect present invention related to is the pharmaceutical preparation that is used for the treatment of diabetes through nasal mucosa medicine administration, and this pharmaceutical preparation comprises the insulin as active ingredient, is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or other is suitable for medicinal excipient or additive.
What further aspect of the present invention related to is the method for preparation through the pharmaceutical preparation that contains polypeptide compounds of nasal mucosa medicine administration.It comprises with as the polypeptide compounds of active ingredient be selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or other is suitable for medicinal excipient or additive mixes.
Further aspect of the present invention relates to is the method for preparation through the pharmaceutical preparation of the insulin-containing of nasal mucosa medicine administration, and it comprises the insulin as active ingredient is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or other is suitable for medicinal excipient or additive mixes.
According to the present invention, used term " polypeptide compounds " is the insulin that for example is selected from cattle, pig or synthetic among the present invention, the polypeptide compound of calcitonin, hirudin, glucagon, vassopressin, prolactin antagonist, growth hormone, thyrotropin, thyroliberin, interferon etc.
Term " taurine alkali metal salt " used in absorption enhancer of the present invention is as sodium, potassium salt etc.; The term that occurs in the absorption enhancer of the present invention " hyaluronic acid alkali metal salt " is as sodium, potassium salt etc.
The term of Shi Yonging " insulin " comprises from the natural insulin of animal (as cattle, pig etc.) or the insulin of synthetic in the present invention.
The term of Shi Yonging " diabetes " is meant I type and type in the present invention.
According to the present invention, of the present invention through nasal mucosa medicine administration the pharmaceutical preparation that contains polypeptide compounds or use with liquid drops or liquid spray form through the pharmaceutical preparation of the insulin-containing of nasal mucosa medicine administration.
According to the present invention, of the present invention through nasal mucosa medicine administration the pharmaceutical preparation that contains polypeptide compound or be human through the subject of the pharmaceutical preparation of the insulin-containing of nasal mucosa medicine administration.
Further, being characterized as of the pharmaceutical preparation that contains polypeptide compounds through nasal mucosa medicine administration of the present invention: pharmaceutical preparation of the present invention comprises 0.01～20w/v% taurine or its alkali metal salt or its C
1-6Arrcostab, or 0.01～10w/v% hyaluronic acid or its alkali metal salt, or their mixture are as absorption enhancer.
According to the present invention, the present invention is depended on order of severity of patient's age, body weight, health and disease etc. through the application dosage of the pharmaceutical preparation that contains polypeptide compounds of nasal mucosa medicine administration.According to the present invention, the pharmaceutical preparation that contains polypeptide compounds through nasal mucosa medicine administration of the present invention can single dose or the use of multiple dose form.
According to the present invention, it is active and nasal mucosa do not found zest or other untoward reaction that pharmaceutical preparation of the present invention demonstrates excellent drug, and therefore, pharmaceutical preparation of the present invention is a kind of good pharmaceutical preparation that mucosa is administered systemically of passing through.
Following experimental example and preparation example are of the present invention further describing, and they do not mean that any limitation of the invention.
Experimental example
The pernasal preparation of the insulin-containing of the present invention that uses with the nasal drop form is to the blood sugar influence because of the caused rat hyperglycemia of injection alloxan
Material
Animal: the Wistar rat, male, body weight 200-220g, available from Military Medical Science Institute's animal center, the quality certification number: No. the 052nd, capital moving pipe matter word (1994)
The pharmaceutical preparation of insulin-containing of the present invention; Dosage is respectively 10IU insulin/kg, 5IU insulin/kg and 2.5IU insulin/kg
Reagent and instrument:
Alloxan: lot number: FL0610021153, commercially available, Hong Kong produces.
UV265 ultraviolet-visible spectrophotometer: Japan
Method:
Get above-mentioned healthy rat fasting, after (freely drinking water 24) hour, intravenous injection alloxan saline solution 40mg/Kg, inject fasting once more (freely drinking water) in back 36 hours, begin test after 12 hours, when beginning to test, after anaesthetizing by 30mg/Kg lumbar injection pentobarbital sodium, every rat gets blood, measure blood glucose, be divided into the blank group at random, model group and administration group.The group of blank group for not injecting alloxan.Blank group and model control group splash into not the present invention of insulin-containing in nasal cavity and are subjected to reagent thing preparation, and dosage is: 10 μ l/100g; The administration group splashes into dosage with equal-volume (10 μ l/100g) to nasal cavity and is respectively 10IU insulin/kg, and the present invention of 5IU insulin/kg and 2.5IU insulin/kg is subjected to reagent thing preparation.Each group is 1,2,3,4 hour measuring blood sugar of blood extracting value after administration all, compares, and the results are shown in following table 1
Table 1: the effect of the rat hyperglycemia that alloxan is caused through the insulin-containing nasal drop of nasal mucosa medicine administration
1 hour group dosage number of animals blood sugar lowering blood sugar lowering value blood sugar lowering percentage rate after the administration
(only) animal, (%), (mg/dl), (%) blank group 10 μ l/100g 10 60 5.9 ± 3.1 8.5 ± 5.1 model group, 10 μ l/100g 10 60 27.1 ± 16.9 11.3 ± 8.7 administration group 10IU/Kg, 10 100 53.3 ± 17.5 18.8 ± 7.3 administration group 5IU/Kg, 10 100 46.0 ± 20.7 17.1 ± 7.8 administration group 2.5IU/Kg 10 100 36.7 ± 17.0 13.2 ± 6.3
Table 1 (continuing)
2 hours group dosage number of animals blood sugar lowering blood sugar lowering value blood sugar lowering percentage rate after the administration
(only) animal (%) is (%) blank group 10 μ l/100g 10 60 8.1 ± 4.6 11.0 ± 6.3 model group, 10 μ l/100g 10 30 6.2 ± 5.5 1.9 ± 1.6 administration group 10IU/Kg, 10 100 89.2 ± 44.2 29.6 ± 10.9 administration group 5IU/Kg, 10 100 59.3 ± 32.0 21.4 ± 10.0 administration group 2.5IU/Kg 10 100 48.6 ± 37.6 16.8 ± 11.2 (mg/dl)
Table 1 (continuing)
Give 3 hours group dosages of medicine number of animals (only) blood sugar lowering blood sugar lowering value blood sugar lowering percentage
Animal, (%), (mg/dl) rate, (%) blank group 10 μ l/100g 10 30 5.1 ± 2.1 7.2 ± 3.0 model group, 10 μ l/100g 10 20 9.8 ± 9.7 2.6 ± 1.8 administration group 10IU/Kg, 10 100 75.6 ± 51.8 24.3 ± 13.9 administration group 5IU/Kg, 10 90 46.1 ± 22.6 16.6 ± 6.8 administration group 2.5IU/Kg 10 80 43.8 ± 35.9 14.9 ± 11.6
Table (continuing)
4 hours group dosage number of animals (only) blood sugar lowering blood sugar lowering value blood sugar lowering percentages after the administration
Animal, (%), (mg/dl) rate, (%) blank group 10 μ l/100g 10 000 model group 10 μ l/100g 10 000 administration group 10IU/Kg 10 100 56.3 ± 53.6 16.8 ± 15.9 administration group 5IU/Kg 10 80 19.3 ± 10.8 6.8 ± 3.5 administration group 2.5IU/Kg 10 80 31.2 ± 29.8 10.4 ± 9.3
Annotate: IU refers to iu.
The pharmaceutical preparation that is shown insulin-containing of the present invention by data in the table 1 can effectively be absorbed and produced ideal blood sugar decreasing effect by nasal mucosa.
Preparation embodiment 1: by the pharmaceutical preparation of nasal mucosa medicine administration
Prescription:
The composition consumption
Insulin 20000IU
Taurine 2g
0.1N hydrochloric acid or 0.1N sodium hydroxide are an amount of
Ethyl hydroxybenzoate 0.03g
Distilled water adds to 100ml
Add an amount of distilled water in above-mentioned taurine, ethyl hydroxybenzoate, heating makes its dissolving, after the cooling; transfer pH to 7 with 0.1N hydrochloric acid or 0.1N sodium hydroxide, add above-mentioned insulin then, after the dissolving; filtration sterilization, gained solution are sub-packed in the special cillin bottle of sterilization.
Preparation embodiment 2: by the pharmaceutical preparation of nasal mucosa medicine administration
Prescription:
The composition consumption
Insulin 20000IU
Hyaluronic acid 0.5g
0.1N hydrochloric acid or 0.1N sodium hydroxide are an amount of
Ethyl hydroxybenzoate 0.03g
Distilled water adds to 100ml
Add an amount of distilled water in above-mentioned hyaluronic acid, ethyl hydroxybenzoate, heating makes its dissolving, after the cooling, transfer pH to 7 with 0.1N hydrochloric acid or 0.1N sodium hydroxide, add above-mentioned insulin then, after the dissolving, filtration sterilization, gained solution are sub-packed in the special cillin bottle of sterilization.
Preparation embodiment 3: by the pharmaceutical preparation of nasal mucosa medicine administration
Prescription:
The composition consumption
Insulin 20000IU
Taurine 2g
Hyaluronic acid 1g
0.1N hydrochloric acid or 0.1N sodium hydroxide are an amount of
Ethyl hydroxybenzoate 0.03g
Distilled water adds to 100ml
Add an amount of distilled water in above-mentioned taurine, hyaluronic acid, ethyl hydroxybenzoate, heating makes its dissolving, after the cooling; transfer pH to 7 with 0.1N hydrochloric acid or 0.1N sodium hydroxide, add above-mentioned insulin then, after the dissolving; filtration sterilization, gained solution are sub-packed in the special cillin bottle of sterilization.
Claims (15)
1. by the pharmaceutical preparation of nasal mucosa medicine administration, the polypeptide compounds that it comprises as active ingredient is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or be suitable for medicinal other excipient or additive.
2. the pharmaceutical preparation of claim 1, wherein said polypeptide compounds is selected from insulin, calcitonin, hirudin, glucagon, vassopressin, prolactin antagonist, growth hormone, thyrotropin, thyroliberin, interferon.
3. the pharmaceutical preparation of claim 1, wherein said polypeptide compound are insulin.
4. the pharmaceutical preparation of claim 1, wherein this pharmaceutical preparation is used with drop or spray form.
5. the pharmaceutical preparation of claim 1 is characterized in that: said preparation contains 0.01-20w/v% taurine or its alkali metal salt or its C
1-6Arrcostab.
6. the pharmaceutical preparation of claim 1 is characterized in that said preparation contains hyaluronic acid or its alkali metal salt of 0.01-10w/v%.
7. the pharmaceutical preparation of claim 1 is characterized in that said preparation contains 0.01-20w/v% taurine or its alkali metal salt or its C
1-6The hyaluronic acid of Arrcostab and 0.01-10w/v% or its alkali metal salt.
8. claim 1, the pharmaceutical preparation that 5-7 is arbitrary, wherein said alkali metal salt is sodium or potassium salt.
9. by the pharmaceutical preparation that is used for the treatment of diabetes of nasal mucosa medicine administration, it comprises that insulin is selected from taurine or its alkali metal salt or its C
1-6Arrcostab, hyaluronic acid or its alkali metal salt, or the absorption enhancer of their mixture, and/or be suitable for medicinal other excipient or additive.
10. the pharmaceutical preparation of claim 9, wherein this pharmaceutical preparation is used with drop or spray form.
11. the pharmaceutical preparation of claim 9, wherein said insulin comprise from pig, the insulin of cattle or synthetic.
12. the pharmaceutical preparation of claim 9, its described diabetes comprise I type and type.
13. the pharmaceutical preparation of claim 9 is characterized in that said preparation contains 0.01-20w/v% taurine or its alkali metal salt or its C
1-6Arrcostab.
14. the pharmaceutical preparation of claim 9 is characterized in that said preparation contains hyaluronic acid or its alkali metal salt of 0.01-10w/v%.
15. the pharmaceutical preparation of claim 9 is characterized in that said preparation contains 0.01-20w/v% taurine or its alkali metal salt or its C
1-6The hyaluronic acid of Arrcostab and 0.01-10w/v% or its alkali metal salt.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98108852A CN1065141C (en) | 1998-05-20 | 1998-05-20 | Medicine preparation administrated through nasal mucosa |
| EP99912088A EP1079801A1 (en) | 1998-05-20 | 1999-04-01 | A pharmaceutical formulation for nasal administration |
| JP2000549208A JP2002515416A (en) | 1998-05-20 | 1999-04-01 | Pharmaceutical preparations for nasal administration |
| AU30550/99A AU3055099A (en) | 1998-05-20 | 1999-04-01 | A pharmaceutical formulation for nasal administration |
| PCT/JP1999/001704 WO1999059543A1 (en) | 1998-05-20 | 1999-04-01 | A pharmaceutical formulation for nasal administration |
| US09/674,519 US6623732B1 (en) | 1998-05-20 | 1999-04-01 | Pharmaceutical formulation for nasal administration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98108852A CN1065141C (en) | 1998-05-20 | 1998-05-20 | Medicine preparation administrated through nasal mucosa |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1235846A true CN1235846A (en) | 1999-11-24 |
| CN1065141C CN1065141C (en) | 2001-05-02 |
Family
ID=5219789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98108852A Expired - Lifetime CN1065141C (en) | 1998-05-20 | 1998-05-20 | Medicine preparation administrated through nasal mucosa |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2002515416A (en) |
| CN (1) | CN1065141C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006066500A1 (en) * | 2004-12-20 | 2006-06-29 | Peixue Ling | The preparation process of quinazoline derivatives and application for the manufacture for the treatment of tumor disease |
| CN112516123A (en) * | 2015-12-25 | 2021-03-19 | 北京乳凝创智生物技术研发中心（有限合伙） | Health-care product external preparation |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2671381B2 (en) * | 1988-05-23 | 1997-10-29 | 藤沢薬品工業株式会社 | Eye drops |
| JPH02104531A (en) * | 1988-10-14 | 1990-04-17 | Toyo Jozo Co Ltd | Physiologically active peptide composition for nasal application |
| JP2911496B2 (en) * | 1989-09-11 | 1999-06-23 | 帝國製薬株式会社 | Highly absorbable vaginal agent containing bioactive polypeptide |
| JP2951681B2 (en) * | 1990-02-23 | 1999-09-20 | 株式会社資生堂 | Pharmaceutical composition for transmucosal administration |
| GB9020544D0 (en) * | 1990-09-20 | 1990-10-31 | Sandoz Ltd | Improvements in or relating to organic compounds |
-
1998
- 1998-05-20 CN CN98108852A patent/CN1065141C/en not_active Expired - Lifetime
-
1999
- 1999-04-01 JP JP2000549208A patent/JP2002515416A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006066500A1 (en) * | 2004-12-20 | 2006-06-29 | Peixue Ling | The preparation process of quinazoline derivatives and application for the manufacture for the treatment of tumor disease |
| CN112516123A (en) * | 2015-12-25 | 2021-03-19 | 北京乳凝创智生物技术研发中心（有限合伙） | Health-care product external preparation |
| CN112516123B (en) * | 2015-12-25 | 2022-07-19 | 北京乳凝创智生物技术研发中心（有限合伙） | Health-care product external preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1065141C (en) | 2001-05-02 |
| JP2002515416A (en) | 2002-05-28 |
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