CN1471922A - Spray contaniing heparin and lipoid, preparing method thereof - Google Patents
Spray contaniing heparin and lipoid, preparing method thereof Download PDFInfo
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- CN1471922A CN1471922A CNA031124372A CN03112437A CN1471922A CN 1471922 A CN1471922 A CN 1471922A CN A031124372 A CNA031124372 A CN A031124372A CN 03112437 A CN03112437 A CN 03112437A CN 1471922 A CN1471922 A CN 1471922A
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- heparin
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Abstract
A spray for treating bronchial asthma, anoxic plumonary hypertension, pulmonary thromboembolism, etc contains heparin and phosphatide. It is applied to lung via trachea by quantitative pump or ultrasonic atomizer. Its advantage is high curative effect.
Description
The present invention relates to spray that contains heparin class and phospholipid and preparation method thereof.
Heparin is a mucopolysaccharide class biochemical drug, for many years, always as anticoagulant by clinical practice.In recent years along with the further of basis and clinical research gos deep into, proved that heparin has multiple biological activity and pharmacological action, except anticoagulant, thromboembolism preventing effect, also have antiinflammatory, antiallergic, immunomodulating, antiviral and anti-tumor activity, multiple disease is had therapeutical effect.For example heparin all has certain therapeutical effect to pulmonary disease such as bronchial asthma, hypoxic pulmonary hypertension, pulmonary thrombo-embolic disease, pulmonary heart disease, pneumonia.Enter air flue after the heparin atomizing sucks, can slowly be discharged behind the macrophage phagocytic again, action temperature and lasting is a kind of administering mode safely and effectively, both can be used for the treatment of pulmonary disease, also can be used as the method for whole body administration.Experiment shows that the Cavia porcellus atomizing sucks heparin 1042u/kg clotting time is not had obvious influence; The mice atomizing sucks heparin 1042u/kg does not have obvious influence to its arteria caudalis bleeding time, illustrates that the hemorrhage side effect of this administering mode is little.
Phospholipid is that (PS extensively is present in alveolar and airway surface to pulmonary surfactant, and the normal physiological function of keeping lung is played an important role for Pulmonary Surfactant, major function composition PS).Recent study shows that PS is its phospholipid composition particularly, has for inflammatory reaction normal and the damage lung and emphasizes to save function, and certain antiinflammatory action is arranged; Discover that for the asthmatic guinea pigs lung-douching fluid wherein protein content is higher by 350% than normal group, content of phospholipid does not have significant difference, and surface activity obviously descends, and shows surface activity and albumen/phospholipid ratio significant correlation.When pulmonary disease shows effect, suitably replenish phospholipid composition, can play a role to the recovery of pulmonary function.In addition, phospholipid is a kind of well behaved surfactant, enter trachea and lung after, help the mucous removing of respiratory tract, thereby help the treatment of pulmonary disease such as asthma.
The objective of the invention is: a kind of spray that contains heparin and phospholipid is provided, and said preparation can be used for treating bronchial asthma, ischemic pulmonary hypertension, pulmonary thrombo-embolic disease or other pulmonary disease, in particular for THE TREATMENT OF BRONCHIAL ASTHMA.
Heparin is meant heparin and its esters or other the pharmaceutically useful derivant of molecular weight between 500～50000 among the present invention.Refer in particular to heparin sodium, calciparine, low molecular sodium heparin and low molecular heparin calcium.
Phospholipid is meant phosphatidylcholine (lecithin), PHOSPHATIDYL ETHANOLAMINE (cephalin) or its pharmaceutically useful derivant among the present invention.Refer in particular to phosphatidylcholine (lecithin).
The spray that the present invention relates to can contain any conventional adjuvant and additive that is used in usually in the pulmonary administration preparation, comprises antibiotic antiseptic, antioxidant, stabilizing agent, emulsifying agent, helps absorbent, correctives, buffer agent and isotonic agent etc.
Preferred spray can contain the pharmacological component that can be used for the pulmonary disease treatment, as the effective ingredient of bronchodilators, anti-inflammatory drug, Claritin, immunoregulation medicament or other treatment pulmonary disease.Wherein bronchodilators comprises albuterol, terbutaline, and anti-inflammatory drug comprises how beclometasone, cloth ground get, and Claritin comprises sodium cromoglicate, ketotifen, and immunoregulation medicament comprises the Bacillus typhi lipopolysaccharide.
Inhalation after spray involved in the present invention can adopt instruments such as ultrasound atomizer with medical liquid atomizing; Inhalation after also can adopting manual pump with medical liquid atomizing, as the Microhaler suction apparatus administration of adopting German Fei Fu company to produce.
The prescription of spray involved in the present invention and scope of medication are: in 100 milliliters, wherein contain heparin 2 * 10
4～2 * 10
6Unit (or Low molecular heparin 1 * 10
4～1 * 10
6Anti-FXa unit), phosphatidase 10 .1～10.0 grams, and contain antibiotic antiseptic ethyl hydroxybenzoate 0.03～0.15 gram or chlorobutanol 0.5 gram, antioxidant vitamin E 0.01～0.20 gram or sodium sulfite 0.1～0.5 gram, emulsifier tween-80 0.1～4.0 gram waits the phosphate buffer of pharmaceutic adjuvant and etoh solvent, propylene glycol and PH 6～8.
Spray preparing process involved in the present invention is: in 100 milliliters, phospholipid and the fat-soluble adjuvant of getting recipe quantity are dissolved in 1～10 milliliter of ethanol, add phosphate buffer and be diluted to about 80 milliliters, the heparin class and the water soluble adjuvant that add recipe quantity, stirring and dissolving adds phosphate buffer to 100 milliliter promptly.
Spray preparing process involved in the present invention also can be: in 100 milliliters, adopt ultrasonic method that phospholipid is scattered in the phosphate buffer, add heparin class and adjuvant, stirring and dissolving adds phosphate buffer to 100 milliliter promptly.
To further illustrate the present invention in following implementation column, these embodiment only are used to the present invention is described and to the present invention without limits.
Embodiment 1
Preparation can be adopted the liquid preparation of instrument administration such as ultrasound atomizer, and concrete operations are as follows: get lecithin 0.25 gram, and vitamin E 0.03 gram, tween 80 0.3 gram is dissolved in 5 milliliters of ethanol, adds phosphate buffer to about 80 milliliters, adds calciparine 5 * 10
4Unit (or low molecular heparin calcium 2.5 * 10
4Anti-FXa unit), ethyl hydroxybenzoate 0.03 gram, stirring and dissolving adds phosphate buffer to 100 milliliter again.
Embodiment 2
Preparation can be adopted the liquid preparation of dosed administration pump administration, and concrete operations are as follows: get lecithin 1.0 gram, vitamin E 0.05 gram, tween 80 1.0 grams and be dissolved in 10 milliliters of ethanol, add phosphate buffer to about 90 milliliters, add heparin sodium 1 * 10
6Unit (or low molecular sodium heparin 0.5 * 10
6Anti-FXa unit), ethyl hydroxybenzoate 0.05 gram, stirring and dissolving adds water to 100 milliliters promptly again.
Embodiment 3
Get lecithin 5.0 gram ultra-sonic dispersion in 80 ml phosphate buffers, add heparin sodium 1 * 10
6Unit (or low molecular sodium heparin 0.5 * 10
6Anti-FXa unit), sodium sulfite 0.2 gram, ethyl hydroxybenzoate 0.05 gram, stirring and dissolving adds phosphate buffer to 100 milliliter.
Embodiment 4
Test preparation with preparation: get lecithin 2.5 grams, vitamin E 0.3 gram, tween 80 3.0 grams are dissolved in 50 milliliters of ethanol, add phosphate buffer to about 800 milliliters, add calciparine 5 * 10
5Unit (or low molecular heparin calcium 2.5 * 10
5Anti-FXa unit), ethyl hydroxybenzoate 0.3 gram, stirring and dissolving adds phosphate buffer to 1000 milliliter and through the filtering with microporous membrane of 0.45 μ m promptly again.
Case is selected and grouping: through the asthma attack phase of clinical definite patient's 51 examples, and male 23 examples, women 28 examples at 23～69 years old age, are divided into treatment group (27 example) and matched group (24 example) at random.The treatment group gives 20 milliliters of ultrasonic atomizatios of liquid preparation of the present invention and sucks except that conventional therapy, and 1 time on the one, 7 is a course of treatment; The matched group conventional therapy.
Observation of curative effect: measuring lung function index before and after the treatment is 1s FEC (FEV
1) and 1s FEC/expiration vital capacity (FEV
1/ FVC); Curative effect judging standard is breathed the standard that sick association of system asthma group is formulated according to Chinese Medical Association.
Result of the test: two groups of patients all have clear improvement in treatment back pulmonary function, but the improvement of treatment group obviously is better than matched group; And the effective percentage of treatment group is apparently higher than matched group (P＜0.01).
Table 1 liang group patients clinical curative effect
The group example number clinic control produce effects invalid effective percentage (%) that takes a turn for the better
Treatment organizes 27 10 16 10 96
Matched group 24 3 14 43 71
Lung function parameter variation before and after the table 2 liang group patient (x ± s)
Group time FEV
1(L) FEV
1/ FVC (%)
Treatment group treatment preceding 1.39 ± 0.59 53.85 ± 12.10
(n=27) the treatment back 2.46 ± 0.61 77.92 ± 8.81
Treatment of control group preceding 1.40 ± 0.63 54.91 ± 11.47
(n=24) the treatment back 1.88 ± 0.57 67.03 ± 8.95
Claims (7)
1. the spray of a pulmonary administration is characterized in that the preparation basic comprising is heparin, phospholipid and adjuvant.
2. the described spray of claim 1 is characterized in that heparin is meant heparin and its esters or other the pharmaceutically useful derivant of molecular weight between 500～50000.Refer in particular to heparin sodium, calciparine, low molecular sodium heparin and low molecular heparin calcium.
3. the described spray of claim 1 is characterized in that phospholipid is meant phosphatidylcholine (lecithin), PHOSPHATIDYL ETHANOLAMINE (cephalin) and pharmaceutically useful derivant thereof.Refer in particular to phosphatidylcholine (lecithin).
4. the described spray of claim 1 is characterized in that wherein containing heparin 2 * 10 in 100 milliliters
4～2 * 10
6Unit (or Low molecular heparin 1 * 10
4～1 * 10
6Anti-FXa unit), phosphatidase 10 .1～10.0 grams, and contain antibiotic antiseptic ethyl hydroxybenzoate 0.03～0.15 gram or chlorobutanol 0.5 gram, antioxidant vitamin E 0.01～0.20 gram or sodium sulfite 0.1～0.5 gram, the phosphate buffer of emulsifier tween-80 0.1～4.0 gram and etoh solvent, propylene glycol and PH 6～8.
5. the described spray of claim 1 is characterized in that can adding pharmacological component as required: the effective ingredient of bronchodilators, anti-inflammatory drug, Claritin, immunoregulation medicament or other treatment pulmonary disease.
6. the described spray preparing process of claim 1 is characterized in that in 100 milliliters, gets lecithin 1.0 gram, vitamin E 0.05 gram, tween 80 1.0 grams and is dissolved in 10 milliliters of ethanol, adds phosphate buffer to about 90 milliliters, adds heparin sodium 1 * 10
6Unit (or low molecular sodium heparin 0.5 * 10
6Anti-FXa unit), ethyl hydroxybenzoate 0.05 gram, stirring and dissolving adds water to 100 milliliters promptly again.
7. the described spray preparing process of claim 1 is characterized in that in 100 milliliters, and also desirable lecithin 5.0 gram ultra-sonic dispersion add heparin sodium 1 * 10 in 80 ml phosphate buffers
6Unit (or low molecular sodium heparin 0.5 * 10
6Anti-FXa unit), sodium sulfite 0.2 gram, ethyl hydroxybenzoate 0.05 gram, stirring and dissolving adds phosphate buffer to 100 milliliter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031124372A CN1471922A (en) | 2003-06-24 | 2003-06-24 | Spray contaniing heparin and lipoid, preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031124372A CN1471922A (en) | 2003-06-24 | 2003-06-24 | Spray contaniing heparin and lipoid, preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1471922A true CN1471922A (en) | 2004-02-04 |
Family
ID=34152426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031124372A Pending CN1471922A (en) | 2003-06-24 | 2003-06-24 | Spray contaniing heparin and lipoid, preparing method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN1471922A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109260181A (en) * | 2017-07-17 | 2019-01-25 | 北京盈科瑞创新药物研究有限公司 | Heparin nebulization sucking pharmaceutical solutions and preparation method thereof |
-
2003
- 2003-06-24 CN CNA031124372A patent/CN1471922A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109260181A (en) * | 2017-07-17 | 2019-01-25 | 北京盈科瑞创新药物研究有限公司 | Heparin nebulization sucking pharmaceutical solutions and preparation method thereof |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
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