CN1366880A - Sophorcarpidine alkaloid and decongestant compound medicine and its preparation method - Google Patents
Sophorcarpidine alkaloid and decongestant compound medicine and its preparation method Download PDFInfo
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Abstract
The compound medicine preparation mainly for curing the diseases of acute and chronic rhinitis, nasal sinusitis nasal obstruction, allergic rhinitis and upper respiratory tract congestion is formed from (wt%) 0.16-1.34% of sophocarpidine alkaloid, 0.1-1.0% of decongestant and other auxiliary material and solvent. Said invention also can be made into oral dosage form, including tablet or capsule, every tablet or every capsule contains, 40-80 mg of sophocarpidine alkaloid and 20-60 mg of decongestant, and its optimum dosage form is aerosol. Said invention also provides the preparation process of said compound aerosol.
Description
Technical field
The present invention relates to medicine, refer to a kind of matrine alkaloid and Decongestant combination drug especially, the invention still further relates to the manufacture method of these medicaments.
Background technology
Matrine alkaloid system is the similar alkaloid of chemical constitution of representative with the matrine, and they extensively are present in leguminous plant Radix Sophorae Flavescentis (Sophora flavescens Ait.), Herba Sophorae alopecuroidis (S.alopecuroides L.) and the root of subprostrate sophora (S.subprostrata Chun etT.Chen).It is the framing structure of representative that matrine alkaloid has with the matrine, promptly belongs to tetracyclic quinolizine pyridine class (quinolizidine), and molecular skeleton can be regarded the body that condenses of two quinolizine pyridine rings, the chemical structural formula of the formula I matrine of face as follows as.
Matrine alkaloid comprises matrine (matrine), oxymatrine (oxymatrine), aloperine (aloperine), sophocarpine (sophocarpine), sophoridine (sophoridine), sophoranol alkali (sophoranol), sophoramine (sophoranine), oxygen sophocarpine (oxysophocarpine) etc.Also comprise the △ that the foreign scholar reports
13-deoxidation sophoridine (△
13-dehydrosophoridine), △
7-deoxidation sophoramine (△
7-dehydrosophoramine), isosophoramine alkali (isosophoramine) and neosophoramine alkali (neosophoramine) etc. (referring to Ueno A, et al.Chen Pharm Bull, 1978,26 (6): 1832).
China was studied the aspects such as pharmacodynamics, pharmacokinetics, toxicology and clinical practice of matrine alkaloid since the seventies.Especially in recent years along with new science and technology development, in the process of research and use matrine, found that further it has various pharmacological activities and clinical function both at home and abroad, and safe and effective, caused people's extensive attention and interest.
Now be summarized as follows with regard to relating to the relevant effect of the present invention:
Effects such as that matrine alkaloid has is significantly antibiotic, antiviral, antiinflammatory, antiallergic action, analgesia, calmness and cooling.Especially to G
+Coccus G
-Bacillus and bottleneck throat common virus CB, Adv, Rsv and influenza, parainfluenza virus all have the obvious suppression effect, in treatment allergy, anaphylactoid rhinitis and bronchial asthma and asthmatic bronchitis significant curative effect is arranged all, and to the nasal mucosa nonirritant.Analgesic activity is apparent in view, and safety range is bigger.
Known medicine preparation such as the anti-inflammatory suppository for gynecopathy that contains matrine alkaloid is raw material with the matrine exactly, is used for the treatment of gynecological inflammation, and these product are recorded by Ningxia Hui Autonomous Region's drug standard (version in 1986).Ministry of Health of the People's Republic of China's matrine injection ministry standard in 1993, it is unusual etc. that clearly these product also are used to recover the glutamate pyruvate transaminase of chronic active liver-fire, chronic animal migration hepatitis and bilirubin.The accurate font size new drug of matrine as the prophylactic treatment tumor " steps clear injection ", has produced and has asked the city.This excavates the new drug of coming out from motherland's medicine precious deposits, under study for action, find that constantly it is that multiple efficacies is arranged, and is promising new drug.
Decongestant among the present invention promptly refers to the sudabid hydrochlorate.Sudabid (Pseudoephedrine) claim pseudoephedrine again, or claim d-pseudephedrine, is the optical isomer of ephedrine.Pseudoephedrine is a sympathomimetic, and is main by stimulating SNE to discharge norepinephrine, plays sympatheticomimetic action with indirect mode.Its pressor effect has certain selectivity, mainly shrinks the upper respiratory tract mucosa blood vessel.For a long time, China then removes as the puppet product in the ephedrine separation pseudoephedrine only with the ephedrine hyoscine.Yet foreign study proves, though pseudoephedrine is weaker than ephedrine to the relexation of bronchial smooth muscle and the intensity of vasoconstriction effect, but it is lighter than ephedrine to untoward reaction such as heart, blood pressure and nervus centraliss, diseases such as the contraction that is used for the upper respiratory tract blood vessel, elimination nasopharynx part mucous hyperemias, curative effect is better than ephedrine, especially compound preparation is widely used in illness such as treatment flu, pollinosis, bronchitis, sinusitis and other upper airway allergic responses.One or nine the May 4ths are since year, and the pseudoephedrine of China exports the U.S. always.Pseudoephedrine hydrochlorate, pharmacopeia is all formally recorded in Great Britain and USA, and Chinese Pharmacopoeia nineteen ninety-five version and two ones of versions in 2000 are all recorded.So far, the production kind of the existing more or less a hundred pseudoephedrine list of state such as Great Britain and America, compound preparation.In the flu analgesic of U.S.'s OTC (over-the-counter), pseudoephedrine has become the important compatibility composition with antipyretic analgesic now.Pseudoephedrine has much glamour in world markets.Because allergic rhinitis, flu, otitis, upper respiratory diseases such as pharyngitis, all be accompanied by the clinical symptoms of nasopharynx part and Eustachian tube mucous hyperemia, in view of this class disease of China very general, again in recent ten years, a lot of comparatively careful element tasks aspect pseudoephedrine, have been done, bibliographical information is more, determined curative effect is reliable, side effect can tolerate, and domestic raw material is abundant, and the domestic demand amount is very big, low price, should make full use of, especially raw material is many in China western part, and is significant to exploitation and western economic development, to this, domestic existing many experts and scholars appeal one after another, should bring into play the advantage that China produces pseudoephedrine, pay attention to and quicken pseudoephedrine Products Development and utilization.
Think be ostracised not as good as ephedrine conclusion outside medicine of pseudoephedrine effect in the twenties in 20th century, having a far reaching influence at home almost influenced half a century, may thoroughly eliminate as yet so far.From the twenties in 20th century until now, though at interval middle more than 80 years, but pseudoephedrine is proved to be a good medicine safely and effectively again and again, especially in recent ten years, pseudoephedrine has developed multiple dosage form, in the progress of bioavailability of effective blood drug concentration, pharmacokinetics, slow release formulation or the like further investigation, its effect and safety have been affirmed more.Therefore, English, U.S. and China are all with its income pharmacopeia, also excited simultaneously China pharmacy worker's interest, pharmaceutical factory of the existing Xinhua of China, Xinjiang pharmaceutical factory, Chifeng Pharmaceutics Factory etc., on the basis of reference state external preparation, with pseudoephedrine and acetaminophen, pseudoephedrine and ibuprofen are formed compound preparation, have carried out the development of new drug.The approval already that has enters clinical verification respectively, the New Drug Certificate of acquisition that has and produce certification or gone on the market.However, but generally speaking, clinical and produce the kind of asking the city with regard to present national approved, and abroad to compare, gap is bigger, and is therefore, also very big to the potentiality of its research and development.
Summary of the invention
As can be seen from the above description, though with the matrine is that the matrine alkaloid of representative and the Decongestant that comprises pseudoephedrine all generally are used in medicament separately or with other composition, but never the someone expects this two Alkaloid is combined in a kind of medicament and uses, the present invention is to matrine alkaloid and subtracting towards a large amount of pharmacology of blood agent forefathers, on the basis of pharmacodynamic study, creatively providing a kind of is the medicament that mainly contains effective constituent with matrine alkaloid with subtracting towards these two kinds of alkaloids of blood agent, under the prerequisite of original medicinal efficacy of giving full play to the two, reach the cooperative compensating on the drug effect, make the medicament that is provided have anti-bacteria and anti-virus simultaneously, antiinflammatory, analgesic, effects such as the analgesia and the blood vessel that contracts, be mainly used in acute and chronic rhinitis, sinusitis, allergic rhinitis, nasal obstruction, the quick treatment of illness such as upper respiratory tract hyperemia, can keep respiratory smooth, also can be used for the treatment that has some inkling of a cold, onset is rapid, can give full play in addition and abound with in the raw material matrine alkaloid in China western part and the medicinal characteristic of pseudoephedrine.
Matrine alkaloid and Decongestant combination drug, it is characterized in that containing simultaneously in this medicament matrine alkaloid and Decongestant, and the use amount of the two is on pharmaceutics in the acceptable effective dosage ranges, can be made into said dosage form on any pharmaceutics, as can be made into nasal mist, nasal drop, also can be made as tablet, capsule, oral administered dosage forms such as soft capsule, syrup.
A kind of preferable dosage form of the present invention is a spray, in this spray by weight the percentage composition meter contain matrine alkaloid 0.16～1.34%, Decongestant 0.1～1.0%, preferred matrine alkaloid 0.5～0.7%, Decongestant 0.3～0.5%, all the other are adjuvant and solvent.Adjuvant is 0.01～1.00wt% Mentholum, 5～20% in the above-mentioned spray
Glycerol, sodium chloride 0.50～1.00wt%, preferred 0.03～0.06%wt Mentholum, 7～10%
Glycerol, sodium chloride 0.50～0.70wt%, surplus is an aqueous solvent.
The another kind of dosage form of the present invention is tablet or soft capsule or hard capsule, and every or every capsules contain matrine alkaloid 40～80mg, and Decongestant 20～60mg is preferably matrine alkaloid 60～80mg, Decongestant 40～60mg.
Said matrine alkaloid is to be selected from matrine, oxymatrine, aloperine, sophocarpine, sophoridine, sophoranol alkali, sophoramine, oxygen sophocarpine, △
13-deoxidation sophoridine, △
7-deoxidation sophoramine, isosophoramine alkali and neosophoramine alkali, Decongestant is selected from N-cathine, ephedrine, pseudoephedrine and phenylephrine.
A kind of method for preparing matrine alkaloid and Decongestant compound spray, it is characterized in that taking by weighing matrine alkaloid, Decongestant, sodium chloride, increase the weight of dissolved in distilled water, put ultrasound wave dissolving instrument or in 40～60 ℃ of water-baths, make its dissolving, survey pH and transfer pH to 4.5～6.5 one-tenth liquid A standby with rare HCl dropping;
Get the Mentholum porphyrize and add dissolve with ethanol, it is standby that adding glycerol is mixed into liquid B;
Liquid A is made into 40～60 ℃ in hot bath, jolting limit, limit adds in the liquid B gradually, makes into colourless or faint yellow clear liquid, adds double distilled water to scale, and mixing filters, packing, and illumination-based disinfection gets product.
The foundation and the meaning thereof of the present invention's prescription:
(1) to take into account with anti-bacteria and anti-virus be that principle designs prescription in the present invention, reaches treatments such as both can be used for rhinitis, can be used for common cold treatment again.
Rhinitis, especially acute rhinitis, system is caused by filterable virus (cold virus, parainfluenza virus, rhinovirus) and antibacterial, many earlier with due to the virus, secondary is with bacterial infection, this with virus and bacterial cross-infection, very easily bring out pathological changes and cause chronic rhinitis, sinusitis, otitis media and upper respiratory tract infection.Disease in view of this virus and bacteria cross infection, still does not have at present not only can effectively improve the nasal obstruction stuffiness, not only tool antibiosis and antiviral functions, while can alleviate not only tool side effect but also few specific medicaments such as nasal cavity edema, just be based on this point, the constantly development of the new drug kind of anti-rhinitis, exploitation.
The present invention is the representative matrine alkaloid with the matrine and is the Decongestant compatibility compound recipe of representative with the pseudoephedrine hydrochloride.Owing to adopted an amount of pseudoephedrine hydrochloride to come vasoconstrictive, both can improve the nasal obstruction stuffiness, can reach gentle lasting again, be difficult for causing medicamentous rhinitis; Owing to adopted matrine, can be in the vasoconstrictive effect, the virus of nasal cavity cross infection and antibacterial played effectively kill inhibitory action, the antiinflammatory that had both had, analgesic, analgesic activity can alleviate edema again, cure inflammation.By with two alkaloidal organic assembling in right amount, effects such as anti-bacteria and anti-virus, antiinflammatory, analgesic, the blood vessel that eases pain, contracts have been strengthened, the quick therapeutical effect that not only can be used for symptoms such as acute and chronic rhinitis, sinusitis, allergic rhinitis, nasal obstruction, upper respiratory tract be not smooth, and the treatment that can be used for having some inkling of a cold, onset is rapid.
With regard to flu, medical research shows, everyone can catch a cold all one's life, according to statistics, the people of China annual nearly 75% catches a cold, calculating every year in view of the above will have 900,000,000 people at the row that use coldrex, on average catch a cold 3-4 time for each person every year especially, repeated cold and belong to antibacterial and viral cross infection is very easily to bring out concurrent suppurative tonsillitis more, chronic bronchitis, nephritis, many diseases such as tumor are again the reasons that the state of an illness increases the weight of, because, there have every year thousands of people to die from influenza to be diseases related, is one of old and the common cause of the death of child, and preventing cold has the important clinical meaning.
Coldrex is essentially first of the hospital administration rank, although the medicine of treatment flu is a lot of on the market, in view of flu is caused still do not have any medicine can thoroughly effect a radical cure flu at present mostly by virus, just be based on this point, the new varieties of Coritab constantly are developed, develop.At present coldrex has complexity and limitation in pharmacology on the curative effect, can As the medicine took effect, the symptoms lessened as antibiotic tackles antibacterial, but coldrex still has its clear and definite and positive pharmacology to be worth, and it is being alleviated cold symptoms, is accelerating in the flu rehabilitation " performing meritorious deeds never to be obliterated ".Particularly flu has stronger infectiousness, fever, nasal obstruction, watery nasal discharge, cough, and symptoms such as extremities aching pain make troubles for work, life, and Coritab is still advocated rationally, actively used to brainstrust.Huge in view of population base, disease is multiple strong, and the market space can reach tens billion of units.Show according to investigations again, China 0-14 year child about 3.3 hundred million more than, account for 26.7% of total population, do not belong to the socialized medicine scope, belong to the medicine crowd that purchases at one's own expense, and the popular children disease incidence is on the rise, so the market space of children's cold medicine is also very big, adds illness crowds such as bigger rhinitis and upper airway allergic responses, therefore, new drug of the present invention has bigger market, meets society need.More, great to developing western economic implications because of primary raw material matrine of the present invention, pseudoephedrine hydrochloride derive from western China.
The present invention will have its certain advantage to the development of control rhinitis and flu, and especially after PPA is disabled, it might become one of good medicine very rare.(2) basis and the test of pesticide effectiveness thereof of dosage establishment
1. comprehensive with reference to the U.S. contain single, the relevant documents and materials of compound preparation of pseudoephedrine, science is closed
Reason ground configuration Decongestant (pseudoephedrine hydrochloride) consumption is between the 0.10-1.00%, in case medicine
The generation of rerum natura rhinitis; It is not remarkable to be lower than 0.10% drug effect, is higher than 1.00% and causes medicine easily
Property allergy.
2. with reference to domestic matrine nasal drop clinical treatment allergic rhinitis 30 examples significant curative effect and right is arranged
The nasal mucosa nonirritant, Radix Sophorae Flavescentis aerosol clinical treatment bronchial asthma and asthmatic bronchitis
33 examples spray into 4-6mg at every turn, and majority takes effect in 10min, and holding time reaches 6-10h,
Have that matrine content is the report of 0.447-0.713% in better curative effect and the BIYANLING PIAN.
3. pass through antibacterial especially antiinflammatory, contracted the vasoactive side of tearing open experiment confirm:
(A) matrine has antiinflammatory action (P＜0.05), and pseudoephedrine does not have antiinflammatory effect (P＞0.05);
(B) matrine does not have the blood vessel function of contracting (P＞0.05), and pseudoephedrine has the blood vessel function of contracting
(P＜0.01)；
Promptly after the present invention's combination, existing antiinflammatory action has the blood vessel function of contracting again, has shown the reasonability of formula combination of the present invention.The consumption of having established matrine is between the 0.16-1.34%;
(C) the present invention has infection work in certain external antibacterial and body to clinical isolating pathogenic bacterium
With;
(D) the present invention has also carried out having pharmacodynamic experiment research analgesic, analgesic activity, proves this
Clearly has analgesic, analgesic activity.
4. for reaching the effective and safe therapeutic purposes:
(A) because should having with snotter, nasal mist and nasal drop equate or slightly high osmotic pressure (being equivalent to 0.9% sodium chloride isotonic solution).A series of to contain variable concentrations sodium chloride (pharmaceutical grade) nasal mist (nasal drop) solution of regulating the osmotic pressure effect as follows for the special preparation of the present invention for this reason:
(1) NaCl 0.5％； (2) NaCl 0.7％； (3) NaCl 0.8％；
(4) NaCl 0.9％； (5) NaCl 1.0％。
More than five batch samples make hemolytic test, screen best isosmotic solution, haemolysis does not all appear in the result, proves the prescription solution of above sodium chloride preparation, all close with snotter isosmotic solution.
(B) the mucous pH normal value of nasal cavity is 5.5-6.5; belong to acid; in the nasal cavity inflammation or when anaphylaxis occurring; present alkalescence, even can be easy to the bacterial growth breeding up to pH=9; and can influence the normal activity of vibrissa; therefore, nasal cavity preparation should be made acid solution, and pH value of the present invention is controlled between the 4.5-6.5.
(C) for enough safeties are arranged during use, human body is not caused adverse effect after the absorption, then having carried out repeatedly nasal mucosa irritation test, acute toxicity test and long term toxicity test, is safe from all provable prescription of the present invention of above experiment, does not produce toxicity.(3) adjuvant:
No matter any medicine is Chinese medicine, Western medicine or biochemical medicine, all can not be directly used in human body, must make the appropriate drug preparation, could use performance curative effect, disease preventing and treating.With a kind of medicine, can make multiple dosage form.Preparation of the present invention except above-mentioned two alkaloid principal agents and be equipped with the adjuvant sodium chloride of regulating the snotter osmotic pressure, also is furnished with adjuvant Mentholum (pharmaceutical grade), has refrigerant, lubricated, local analgesia itching-relieving action; Be furnished with adjuvant glycerol (pharmaceutical grade), can increase the viscosity of solution, the time of staying of prolong drug in nasal cavity, this product in vivo again hydrolyzable, be oxidized to nutrient substance.Above preparation makes it to become a kind of appropriate drug preparation.(2) processing technology
Method for making
1, take by weighing matrine 5.0g, pseudoephedrine hydrochloride 3.0g, sodium chloride 5.0g puts in the 1000ml beaker,
Add double distilled water 400ml, put in the ultrasound wave dissolving instrument (or 40～60 ℃ of water-baths) and make its dissolving, add
Double distilled water 400ml is to room temperature, surveys PH and drips with 1mol HCl and transfer PH to 4.5～6.5 one-tenth
Liquid A is standby.
2, get Mentholum 0.3g porphyrize and add 95% ethanol 10ml dissolving, add 100ml glycerol mixing and put
Become liquid B standby in the 1000ml measuring bottle.
3, liquid A is made into 40～60 ℃ in hot bath, jolting limit, limit adds in the liquid B gradually, makes
Become colourless or faint yellow clear liquid, add double distilled water to 1000ml, mixing filters, packing,
Illumination-based disinfection gets product.
The present invention has two big main points most important in technological process and method for making thereof, once the resulting liquid B of second step is added to while stirring gradually (also being general method for making) in the resultant liquid A of first step, and when adding water to 1000ml, Mentholum can be separated out; As not carrying out under 40～60 ℃ of conditions, Mentholum equally also can be separated out, so join liquid A in the liquid B and be essential condition under 40～60 ℃ of conditions, this has constituted the characteristics of processing technology of the present invention.(3) dosage form
Pharmaceutical preparation of the present invention is used with spray, nasal drop and multiple peroral dosage form form.Now the spray with nasal mucosa medicine administration is that representative is summarized as follows:
1, the nasal spray by nasal administration (also claim nasal spray, or nasal spray) is to work as
Before one of the novel form of primary study exploitation in the world.The aerosol apparatus that spray of the present invention is used
Be quantitative aerosol apparatus.System adopts by international ISO 9001 quality authentications [DIN EN ISO
9001], European DIN EN 46001 medicinal apparatus quality authentications [DIN EN 46001] and obtaining
The moral of the medicinal folder of U.S. FDA (Drug Master File) registration-DMF NO.6350
State's phenanthrene is quantitative (0.1ml/ spray) nasal cavity shower nozzle [the FDA Drug Master of (Pfeiffer) company not
File(DMF)NO.6350]。
2, the nasal administration dosage form can be brought into play the systemic treatment effect as injecting medicine-feeding form, gives birth to
Thing availability height.In recent years, along with the exploitation of novel form and dark to the nasal absorption medicine
Go into research, this route of administration of nasal cavity might be brought into play the systemic treatment effect, clinically
Good using value is arranged, so nasal drug delivery system is paid attention to by people gradually.Nasal cavity
The mucosa area of lining has a palm big, can reach the 120-150 square centimeter.Nasal cavity is sticking
Blood vessel under the film is quite abundant, numerous small artery, vein, blood capillary, lymph
Pipe is woven into net, extends in all direction, and after medicine adheres to mucosa, is easy to see through mucosa and advances
Go into blood, and enter systemic blood circulation performance by intracranial vein and cervical region vein and do very soon
With.In addition, on each cell of nose breathing district unnumbered fine hair is arranged, it and intestinal villi
Effect is the same, has very strong absorbent function, and therefore, nasal cavity is to the significant surface of drug absorption
The long-pending first-pass effect that has increased and can avoid the intestinal liver has improved bioavailability of medicament,
The bioavailability that makes the some drugs interanasal administration can reach general again and use near 100%
The medicine purpose.From in June, 1984, carry out whole body therapeutic in the via intranasal application administration that the U.S. holds
International conference and the special topic of NJ USA Luo Jie (Rutger) university press in 1985
Can find out in symposium's data information, nasal drug delivery system really one the treatment on medicine
The effective route of administration that obvious advantage is arranged on moving the learning.Nasal cavity is the individual liposoluble that both had been applicable to
The property be applicable to the effective site that water soluble drug absorbs again.The nasal-cavity administration approach is to many molecules
Amount is rapid and effective less than 1000 drug absorption, can not add any absorption enhancer,
Bioavailability average out to about 70%.If select suitable absorption enhancer, the branch of medicine for use
The son amount also can absorb 6000 or 6000 above persons.Someone has studied tens of kinds of different moleculars
The medicine of amount has proved that in the absorption of nasal cavity molecular weight is biological sharp less than 1000 chemical compound
Expenditure is fine, and more much higher than oral absorption.
3, the nasal administration dosage form can be created high focus drug level, the curative effect height, and instant effect,
Toxic and side effects is little.To rhinitis especially to general cold virus, only on the upper respiratory tract mucosa top layer
Form local actute infection focus, seldom enter blood, to this, with traditional oral administration
Mode is changed into the direct spray deliveries in upper respiratory tract focus position such as nasal membrane, in this medicine
Target position can create other dosage form administration incomparable high focus drug level, can
Cut off the course of disease rapidly as flu and so on, the curative effect height, instant effect, toxic and side effects is little, again can
The effect of performance systemic treatment.
4, the present invention system records molecular weight less than two alkaloid warps of 1000 with pharmacopeia and ministry standard
Scientific and reasonable prescription and form have anti-bacteria and anti-virus, antiinflammatory, analgesic, blood vessel eases pain, contracts
Deng the effect compound recipe nasal spray drug-delivery preparation, its maximum characteristics, because of medicinal liquid directly equably
Be distributed in nasal mucosa, can form high focus drug level, acute and chronic rhinitis, nasal sinuses
Inflammation, allergic rhinitis, nasal obstruction, watery nasal discharge, sneeze, pharyngitis, upper respiratory tract infection and flu
From the beginning of etc. symptom efficient quick-acting therapeutical effect is arranged, can bring into play the systemic treatment effect again and subtract
Few untoward reaction and complication.General medication every day of this product 2-3 time, each 2-3 spray,
2-3 days is a course of treatment.The quantitative nasal cavity of the German Pfeiffer company import that this product will adopt
Shower nozzle, consumption is accurate, and is easy to use, and drug safety is especially to child and unsuitable oral
Patient need not take medicine and have an injection, and brings convenience especially.
(4) relatively
The Class A medication of treatment rhinitis has the ephedrine hydrochloride nasal drop, two nasal sprays of the beclometasone of the restricted use of Class B medication and levocabastine from the national basic medical insurance medicine catalogue of the People's Republic of China (PRC) and Department of Social Security's announcement on May 25th, 2000; The medication of three treatments of ephedrine and Sai Luo azoles quinoline nasal drop and oxymetazoline mist rhinitis is arranged from (2000) " national essential drugs " preparation variety catalogue that two OO of National Drug Administration issued on March 30th, 1.Certainly, also sold other rhinitis medicine on the market.With regard to the congested agent of the alkali of these medicine polyphyly alpha-2-adrenoceptor excitomotor classes in the catalogue and the class medicine of relievining asthma, its therapeutic effect is each has something to recommend him, what have only has the effect of temporary transient elimination symptom to certain rhinitis, the zest that has is big or side effect is bigger, and indication is little, as Decongestant ephedrine hydrochloride nasal drop, can make vasoconstriction and improve nasal obstruction, but can not fit the disease treatment,, and cause medicamentous rhinitis easily again because its concentration reaches 1%.
Different above each the medicine part of the present invention is:
1, composition difference.With two alkaloid compound recipes, the prescription uniqueness, so far, not seeing both at home and abroad has
Identical or similar prescription.
2, indication is big.Existing vasoconstrictive effect can be eliminated symptoms such as nasal obstruction, watery nasal discharge, sneeze rapidly,
Effects such as anti-bacteria and anti-virus, antiinflammatory, antipyretic-antalgic are arranged again, can the efficient acute and chronic for the treatment of quick-actingly
Symptoms such as rhinitis, sinusitis, allergic rhinitis, pharyngitis, upper respiratory tract infection and flu.
3, dosage form is good, the bioavailability height.The curative effect height, instant effect can be cured above chronic disease.
4, medication handy and safe.Nasal administration; Need not have an injection and take medicine.Can not produce medicamentous rhinitis,
Non-stimulated to nasal mucosa, have no side effect or toxic and side effects minimum, the patient all can stand.
5, raw material sources are in domestic western part.To promoting China's Western Economic significant.
(5) enumerate case
On the experiment basis of finishing formulation and technology, quality standard and the basic research of pharmacodynamics toxicology, in line with reference to the way of some country, before declaring Clinical Researches of New Drugs, test on one's body by development person earlier in the new drug development exploitation, provide on probation to volunteer then.Nearly 1000 bottles of the present invention since nineteen ninety-five successively were provided approximately, owing to comparatively disperse, result on trial is difficult to gather comprehensively, the existing introduction that random collecting is arrived wherein 6 for example down:
Example 1: Shen * *, woman, 62 years old, Han nationality, medical personnel.Year surplus trouble sinusitis and allergic rhinitis reach 40, often more than, the nasal obstruction of nose stream yellow thick nasal discharge, wing of nose both sides and head pain throughout the year, agonizing, once in the name well-known doctor of institute of many families such as Concord Hospital, Beijing Tongren Hospital, Friendship Hospital diagnosis and treatment, all do not cure, wherein Concord Hospital did the autoimmune treatment, slightly cured after a while, but scene is not long, and all as before.Nineteen ninety-five rises, and only when concurrent flu, adopts some courses of treatment of the present invention through intermittent, finally the disease of its rhinitis is cured, and until nowadays, existing 6 years, do not see recurrence.
Example 2: fourth * *, man, 28 years old, Han nationality, medicine marketing person.Suffer from sinusitis, allergic rhinitis 11 years, often nose stream yellow thick nasal discharge is more than throughout the year, makes other people dislike well, nasal obstruction, wing of nose both sides and head pain, very painful, once at how tame hospital therapy, all of no avail, naphazoline commonly used only has interim effect, and side effect is big.Because of the nostril stuffiness, need mouth breathing in bed, also easily violate dry mouth and tougue at ordinary times, pharynx and very easily repeated infection of respiratory tract.March calendar year 2001 is through adopting the present invention, using continuously about one month after the time, and rhinitis is good entirely, and nose has not also blocked, and does not see that also nasal mucosa has any damage and untoward reaction.Closely over the past half year, stable normal, do not see recurrence.
Example 3: the king * *, man, 48 years old, Han nationality, administrative general manager.1999 in chance opportunity, because of its flu provides one bottle of the present invention (5ml nasal drop) on probation, the result not only catches a cold quick-acting, what is more important is failed to respond to any medical treatment for a long time to it and worried rhinitis has also obviously taken effect, then this its spy requires to provide the present invention once more, in view of sorry at that time, the out of stock supply and cutting off.
Example 4: Bao * *, man, 64 years old, Han nationality, senior engineer.Long-term often nasal cavity throat inflammation is swollen and ache and fierce cough, execute through multiple medicine and to control, there is no effect, since nineteen ninety-five, all when often falling ill, or when making a noise flu and influenza, adopt the present invention, at once alleviate and then get better very soon, therefore since nineteen ninety-five itself and the whole family thereof, excessive flu, influenza and the upper respiratory tract infection disease of all making a noise.
Example 5: poplar * *, man, 48 years old, Han nationality, medicine marketing person, midsummer in this year, because of pyretic cold or be air conditioning disease, watery nasal discharge, shed tears and have a stuffy nose, cough etc., through adopting when of the present invention, every day 2 times, each 3 sprays, with after BITONG, rhinorrhea not at once, healed entirely less than 2 days.
Example 6: Bao * *, the woman, 4 years old, Han nationality was at kindergarten.The flu, nasal obstruction, tractive current nasal mucus of often making a noise is more than, and child is afraid of to take medicine to have an injection, through adopting the present invention, child just called after medication and tells in second day: " grandfather has used nose drops, does not take medicine and does not have an injection; my nose is rhinorrhea not, and nose has also been ventilated, and thanks grandfather ".(6) embodiment
By the following examples the present invention is described specifically, the matrine in the embodiment of the invention is provided by Ningxia Feng Liyuan biochemical industry Products Co., Ltd, and pseudoephedrine hydrochloride is provided by Chifeng pharmaceutical factory.＜embodiment 1 〉
Get matrine 5.0 grams, pseudoephedrine hydrochloride 3.0 grams, sodium chloride 5.0 grams, Mentholum 0.3 gram, 100 milliliters of glycerol, put in the 1000ml milliliter volumetric flask, it is an amount of to add double distilled water, dissolving, mixing, transfer pH4.5～6.5, add water to scale, mixing is made 5 milliliters of sprays or 5 milliliters of nasal drop after the filtration.Usage: every day, nasal-cavity administration was 2～3 times, and each 2～3 spray or 2～3, and the child considers, and 2～3 days is a course of treatment.＜embodiment 2 〉
Get matrine 13.4 grams, pseudoephedrine hydrochloride 8.0 grams, sodium chloride 10.0 grams, Mentholum 0.3 gram, 100 milliliters of glycerol, put in the 1000ml milliliter volumetric flask, it is an amount of to add double distilled water, dissolving, mixing, transfer pH4.5～6.5, add water to scale, mixing is made 5 milliliters of sprays or 5 milliliters of nasal drop after the filtration.Usage: every day, nasal-cavity administration was 2～3 times, and each 2～3 spray or 2～3, and the child considers, and 2～3 days is a course of treatment.＜embodiment 3 〉
Get matrine 70 gram and fully mix with pseudoephedrine hydrochloride 50 grams, adding mixed with excipients tablet forming or capsule, every or every capsules contain matrine 70mg, pseudoephedrine hydrochloride 50mg.A day oral effective dose is about 1 or 1～6 or 6, preferred 2 or 2～6 or 6 in treatment.Two weeks were a course of treatment.＜embodiment 4 〉
Take by weighing matrine 700 grams, pseudoephedrine hydrochloride 500 grams respectively, add mix homogeneously in the batch can, transfer in system (dripping) the ball machine hopper again, drip system or compacting soft gelatin capsule, every ball contains matrine 70mg, pseudoephedrine hydrochloride 50mg, and usage is with tablet or capsule.
Claims (10)
1, matrine alkaloid and Decongestant combination drug is characterized in that containing matrine alkaloid and Decongestant in this medicament simultaneously, and the use amount of the two is on pharmaceutics in the acceptable effective dosage ranges.
2, matrine alkaloid according to claim 1 and Decongestant combination drug, it is characterized in that said medicament is a spray, in this spray by weight the percentage composition meter contain matrine alkaloid 0.16～1.34%, Decongestant 0.1～1.0%, all the other are adjuvant and solvent.
3,, it is characterized in that in the said spray that the percentage composition meter contains matrine alkaloid 0.5～0.7%, Decongestant 0.3～0.5% by weight according to said matrine alkaloid of claim 2 and Decongestant combination drug.
4,, it is characterized in that said adjuvant is 0.01～1.00wt% Mentholum, 5～20% according to said matrine alkaloid of claim 2 and Decongestant combination drug
Glycerol, sodium chloride 0.50～1.00wt%, surplus is an aqueous solvent.
5,, it is characterized in that said adjuvant is 0.03～0.06wt% Mentholum, 7～10% according to said matrine alkaloid of claim 4 and Decongestant combination drug
Glycerol, sodium chloride 0.50～0.70wt%, surplus is an aqueous solvent.
6, matrine alkaloid according to claim 1 and Decongestant combination drug is characterized in that said medicament is tablet or hard capsule or soft capsule, and every or every capsules contain matrine alkaloid 40～80mg, Decongestant 20～60mg.
7, matrine alkaloid according to claim 6 and Decongestant combination drug is characterized in that every or every capsules contain matrine alkaloid 60～80mg, Decongestant 40～60mg.
8,, it is characterized in that said matrine alkaloid is to be selected from matrine, oxymatrine, aloperine, sophocarpine, sophoridine, sophoranol alkali, sophoramine, oxygen sophocarpine, △ according to each described matrine alkaloid of claim 1 to 7 and Decongestant combination drug
13-deoxidation sophoridine, △
7-deoxidation sophoramine, isosophoramine alkali and neosophoramine alkali, Decongestant is selected from N-cathine, ephedrine, pseudoephedrine and phenylephrine.
9,, it is characterized in that said medicament is a said dosage form on any pharmaceutics according to said matrine alkaloid of claim 1 and Decongestant combination drug.
10, the method for preparing said matrine alkaloid of claim 2 and Decongestant compound spray, it is characterized in that taking by weighing matrine alkaloid, Decongestant, sodium chloride, increase the weight of dissolved in distilled water, put ultrasound wave dissolving instrument or in 40～60 ℃ of water-baths, make its dissolving, survey pH and transfer pH to 4.5～6.5 one-tenth liquid A standby with rare HCl dropping;
Get the Mentholum porphyrize and add dissolve with ethanol, it is standby that adding glycerol is mixed into liquid B;
Liquid A is made into 40～60 ℃ in hot bath, jolting limit, limit adds in the liquid B gradually, makes into colourless or faint yellow clear liquid, adds double distilled water to scale, and mixing filters, packing, and illumination-based disinfection gets product.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101116662B (en) * | 2004-12-10 | 2010-06-02 | 上海第二医科大学附属仁济医院 | Application of sophocarpine in the preparation of medicine for treating adenovirus-caused inflammation |
| CN101134035B (en) * | 2004-12-10 | 2010-06-09 | 上海第二医科大学附属仁济医院 | Application of sophocarpine in the preparing of medicament for treating inflammation caused by influenza B virus |
| CN101953835A (en) * | 2009-07-13 | 2011-01-26 | 上海交通大学医学院附属仁济医院 | Application of sophocarpine in preparing medicaments for treating diseases caused by H5N1 viruses |
-
2002
- 2002-01-23 CN CN 02102499 patent/CN1212116C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101116662B (en) * | 2004-12-10 | 2010-06-02 | 上海第二医科大学附属仁济医院 | Application of sophocarpine in the preparation of medicine for treating adenovirus-caused inflammation |
| CN101134035B (en) * | 2004-12-10 | 2010-06-09 | 上海第二医科大学附属仁济医院 | Application of sophocarpine in the preparing of medicament for treating inflammation caused by influenza B virus |
| CN101953835A (en) * | 2009-07-13 | 2011-01-26 | 上海交通大学医学院附属仁济医院 | Application of sophocarpine in preparing medicaments for treating diseases caused by H5N1 viruses |
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