CN1299680C - Black-white formulation for treating insomnia - Google Patents
Black-white formulation for treating insomnia Download PDFInfo
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- CN1299680C CN1299680C CNB2005100934055A CN200510093405A CN1299680C CN 1299680 C CN1299680 C CN 1299680C CN B2005100934055 A CNB2005100934055 A CN B2005100934055A CN 200510093405 A CN200510093405 A CN 200510093405A CN 1299680 C CN1299680 C CN 1299680C
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- diphenhydramine
- insomnia
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- 206010022437 insomnia Diseases 0.000 title claims abstract description 39
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- 238000002360 preparation method Methods 0.000 claims abstract description 66
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- 229960003987 melatonin Drugs 0.000 claims abstract description 25
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a black-white formulation for treating insomnia and the application of the formulation in the aspect of treating insomnia, adjusting sleep rhythm and reducing time difference reaction. The black-white formulation comprises two single ingredients; a black preparation is taken at night, and a white preparation is taken in the daytime. The formula of the black preparation comprises 5-hydroxytryptophane, melatonine, diphenhydramine or an acid addition salt thereof; the formula of the white preparation comprises aspirin and caffeine. Single technological processing is carried out to 2 to 4 respective raw material medicines of the two single ingredients. The black preparation can achieve the therapeutic effect of the existing various medicines for treating insomnia; the white preparation can eliminate the hangover effect so that a user can guarantee the normal work with conscious mind in the daytime. When the black preparation and the white preparation are used together with convenience and safety, the aims of treating the insomnia, adjusting the sleep rhythm and reducing the time difference reaction can be achieved. The black-white formulation of the present invention is an ideal product of modern pharmaceutical enterprises.
Description
Technical field
The present invention relates to a kind of black/white preparation, be specifically related to the black/white preparation of a kind of Cure for insomnia, adjustment sleep rhythm, minimizing jet lag.
Background technology
The basic definition of insomnia is a sleep disorder, and often is meant and can not obtains normal sleep.Research worker thinks that insomnia is not have enough sleep, or sleeps not deeply, not yet done, generally is rendered as initial insomnia, is interrupted insomnia and three characteristics of terminal point insomnia.Insomnia relation is little once in a while, suffers from the insomnia and have only continuously for a long time can't the person of falling asleep just to calculate.The sickness rate of insomnia is very high, shows according to the foreign data investigation, and the insomnia incidence rate is 32%～35% in the American population, and Japan is 20%.It is also quite a lot that the patient is sent out in China's insomnia, and particularly the number of middle-aged and elderly people appearance insomnia is more.And the foreign statistic numeral shows, the old people insomniac is up to 70%.Human life's 1/3 spends in sleep, and fine sleep is to make alive, the happy and healthy assurance of all the other 2/3 time.Say that gravely insomnia just equals to fritter away one's time. this shows that insomnia is a rather important problem in people's life.
Concerning insomnia patients, it is natural seeking the medicine of effectively sleeping peacefully. in many cases, the reason of insomnia is difficult for finding, and by the sleep disorder International Classification this obstacle is referred to as Primary insomnia, shows as Psychophysiological insomnia or subjective sensation aypnia etc.The method for the treatment of this class insomnia generally includes following two kinds: 1) use sedative hypnotic drug, reach health product for treating; 2) non-drug therapy mainly contains the behavior therapy, relaxation therapy, cognitive therapy and phototherapy etc.But Drug therapy is still present Cure for insomnia main method.
Ideal sedative hypnotic drug should possess following condition: 1) rapid sleep inducing; 2) to not influence of Sleep architecture; 3) drug residue free effect in second day; 4) do not influence memory function, comprise and do not forget symptom; 5) breathing there is not inhibitory action; 6) life-time service does not have drug dependence or drug withdrawal symptom; 7) there is not interaction with ethanol and other drug.But, up to now, also do not have a kind of medicine of sleeping peacefully that meets above-mentioned condition fully.
Summary of the invention
Purpose of the present invention is to provide a kind of curative effect excellence, has no side effect substantially, prepares easyly, does not influence the black/white preparation recipe of the Cure for insomnia of operate as normal life on daytime.
The principle of technical solution of the present invention:
The design creativity of black/white preparation, existing in theory inheritance is also paid attention to pioneering.Learn from other's strong points to offset one's weaknesses, with reference to the sure achievement of finishing through laboratory and clinical research, consider targetedly that fully following several respects carry out prescription design: body endogenous hypnosis material melatonin can be induced the physiological sleep, the toxic and side effects that does not have benzodiazepine, use the people of melatonin Cure for insomnia more and more in recent years, but the melatonin syngignoscism a little less than.5-hydroxyryptophan is next-door neighbour's precursor substance of the neurotransmitter serotonin in the central nervous system.5-hydroxyryptophan can non-specific decarboxylation be converted into 5-hydroxy tryptamine in norepinephrine energy dopaminergic and serotoninergic neuron.Simultaneously, 5-hydroxyryptophan can promote to produce the endogenous melatonin in the body, with exogenous melatonin combined effect, reaches the purpose of improving sleep.Vitamin B
6Have catalytic coenzyme effect, can promote the biosynthesis of central neurotransmitter γ-An Jidingsuan, dopamine, 5-hydroxy tryptamine, further strengthened the effect of Cure for insomnia.Diphhydramine hydrochloride and diphenhydramine citrate have and the equal syngignoscism of hypnosis preparation commonly used, but are not used in the Insomnia therapy of patients with depression.Diphenhydramine disappears in blood rapidly, does not produce toleration.Caffeine can be refreshed oneself, and is used to remove the hangover effect that black preparation brings, and user can guarantee operate as normal on daytime, life with clear-headed brains.Aspirin can prevent platelet aggregation, has reduced because insomnia causes the risk of cardiovascular and cerebrovascular disease.Obey black preparation evening and have a good sleep, obey white preparation daytime, in high spirits.Black/white preparation complements each other, thereby reaches " sleep quality improves entirely ".
Body endogenous hypnosis material melatonin can be induced physiological sleep, does not have the toxic and side effects of benzodiazepine, uses the people of melatonin Cure for insomnia more and more in recent years, but the melatonin syngignoscism a little less than.5-hydroxyryptophan is next-door neighbour's precursor substance of the neurotransmitter serotonin in the central nervous system.5-hydroxyryptophan can non-specific decarboxylation be converted into 5-hydroxy tryptamine in norepinephrine energy dopaminergic and serotoninergic neuron.Simultaneously, 5-hydroxyryptophan can promote to produce the endogenous melatonin in the body, with exogenous melatonin combined effect, reaches the purpose of improving sleep.Vitamin B6 has catalytic coenzyme effect, can promote the biosynthesis of central neurotransmitter γ-An Jidingsuan, dopamine, 5-hydroxy tryptamine, has further strengthened the effect of Cure for insomnia.Diphhydramine hydrochloride and diphenhydramine citrate have and the equal syngignoscism of hypnosis preparation commonly used, but are not used in the Insomnia therapy of patients with depression.Diphenhydramine disappears in blood rapidly, does not produce toleration.Caffeine can be refreshed oneself, and is used to remove the hangover effect that black preparation brings, and user can guarantee operate as normal on daytime, life with clear-headed brains.Aspirin can prevent platelet aggregation, has reduced because insomnia causes the risk of cardiovascular and cerebrovascular disease.Obey black preparation evening and have a good sleep, obey white preparation daytime, in high spirits.Black/white preparation complements each other, thereby reaches " sleep quality improves entirely ".
Technical scheme of the present invention is as follows:
The composition of B﹠W preparation recipe:
(1) the black preparation prescription is formed: 5-hydroxyryptophan: 50-300mg, melatonin: 1-10mg, diphenhydramine or its acid-addition salts: 3-75mg, VB6:0-10mg.
(2) the white preparation prescription is formed: aspirin: 25-200mg, caffeine: 30-150mg.
Its optimum formula is:
(1) the black preparation prescription is formed: 5-hydroxyryptophan: 100mg, melatonin: 3mg, diphenhydramine or its acid-addition salts: 25mg.
(2) the white preparation prescription is formed: aspirin: 50mg, caffeine: 50mg
The acid-addition salts of diphenhydramine can be enumerated: diphhydramine hydrochloride, diphenhydramine citrate, diphenhydramine salicylate, tannin diphenhydramine, lauryl sulphate acid diphenhydramine and sulphuric acid diphenhydramine, wherein particularly preferred acid-addition salts is diphhydramine hydrochloride and diphenhydramine citrate.
Black preparation and white preparation can be produced and be capsule, tablet, granule, powder, pill, granula subtilis, lozenge.Wherein prilling process can adopt general prilling process, for example utilize and contain the solution of water or organic solvent or spray granulation, stirring-granulating method, fluidized granulation method that dispersion liquid carries out, rotate wet granulations such as comminution granulation, rotational flow comminution granulation, and the dry pelletizing methods such as compacting comminution granulation of utilizing powder shape binding agent.Granule, granula subtilis are adjusted particle grain size so that powder can pass through above-mentioned method for making granules, as required, can sift out by sieve, obtain corresponding preparations.In addition, tablet is to be mixed together by powder agent, granula subtilis, granule or pill and formulation additives, compression forming and the corresponding preparations made.And capsule is to utilize powder agent, granula subtilis, granule and small-sized tablet etc. capsule filling machine to be filled in the capsule to make.
Black preparation is made up of 5-hydroxyryptophan, melatonin, diphenhydramine or its acid-addition salts, (VB6) among the present invention, 5-hydroxyryptophan is next-door neighbour's precursor substance of the neurotransmitter serotonin in the central nervous system, can promote to produce in the body endogenous melatonin, with exogenous melatonin combined effect, reach the purpose of improving sleep, act on softly, side effect is little.Melatonin is the synthetic and excretory a kind of hormone of pinus in the human brain, and melatonin can not only improve sleeper effect, and can also regulate, stablize and rebuild physiological rhythm, alleviates the jet lag syndrome.Melatonin is not foreign body as a kind of endogenous material to body, and the half-life is short, and nothing is accumulated, and toxicity is minimum.But a little less than its syngignoscism, also use at present as health food.Diphenhydramine or its acid-addition salts Cure for insomnia are evident in efficacy.Vitamin B6 has catalytic coenzyme effect, can promote the biosynthesis of central neurotransmitter γ-An Jidingsuan, dopamine, 5-hydroxy tryptamine, can more effective improvement sleep with melatonin than single; White preparation is made by aspirin, caffeine, caffeine refreshment, allaying tiredness, curative effect are fast, effective, and aspirin can prevent platelet aggregation, prevent the generation of cardiovascular and cerebrovascular disease, thereby has reduced the patient because insomnia causes the risk of cardiovascular and cerebrovascular disease.The two replenishes mutually, reaches the purpose that increases curative effect, reduces side effect.
Five, simple, the easily manufacturing of composition of the present invention, raw material proves to have no side effect in clinical use for many years.
Six, preparation provided by the invention has following advantage: black preparation is evident in efficacy, can reach in the curative effect of present various Cure for insomnia medicines commonly used, and safe and reliable, side effect is little; Preparation and easy to use.The sleeping ortho sleep structure that soon, do not influence.White preparation reduces hangover effect, adjusts Sleep architecture, makes the patient keep operate as normal on daytime, life with clear-minded head, prevents generation, the minimizing jet lag of cardiovascular and cerebrovascular disease simultaneously.
Seven, took 1 Packing Unit of black preparation before at 9 in patient evening,, can add 1 Packing Unit before ten two of evenings, do not advise taking black preparation after ten two if effect is bad.Take 1 Packing Unit of white preparation early one hour after meal daytime, adds 1 Packing Unit in case of necessity after the lunch break again, but do not advise taking white preparation after at 4 in afternoon.
The specific embodiment:
The preparation of black preparation:
Embodiment one:
1, the 3mg melatonin is dissolved back and 500mg oligomeric xylose mixing granulation with Diluted Alcohol;
2, the 100mg5-oxitriptan is dissolved back and 500mg oligomeric xylose mixing granulation with Diluted Alcohol;
3, the 25mg diphenhydramine is dissolved back and 500mg oligomeric xylose mixing granulation with Diluted Alcohol;
4, with the melatonin granule that obtains, 5-hydroxyryptophan granule, diphenhydramine granule with the magnesium stearate mixing, sneak into lubricant after the drying, the fill capsule promptly.
Embodiment two:
1. with 5-hydroxyryptophan 200mg, melatonin 6mg and vitamin B
66mg granulates drying with Diluted Alcohol dissolving back.
2. mix 75mg diphhydramine hydrochloride, 100mg crystalline cellulose, 700mg lactose, 20mg intersection sodium carboxymethyl cellulose, 50mg light silicon dioxide, add the alcoholic solution of 240mg10% hydroxypropyl cellulose, stir, granulate and drying.
3. with 1,2 gained granule mixings.Tabletting.
Embodiment three:
Take by weighing 50g 5-hydroxyryptophan, 2g melatonin, 6g and vitamin B
6, 10g diphhydramine hydrochloride (above component is used to prepare 1000 bags of granules); the sucrose, 100g starch and the 100g dextrin that add 1420g; make wetting agent with 75% ethanol; granulate with 16 mesh sieves; baking temperature is 60 ℃; time is 2 hours, and dry back gets granule with oscillating granulator 14 mesh sieve granulate, pack packing.
The preparation of white preparation:
Embodiment one:
1, with 50mg caffeine and microcrystalline Cellulose with equivalent incremental method mixing, again with the pregelatinized Starch mix homogeneously, add 5%PVPK30 solution and make soft material, sieve and granulate dry or directly granulate with one-step-granulating method.
2, with 50mg aspirin, ethyl cellulose microcrystalline Cellulose, starch is crossed mix homogeneously behind 80 mesh sieves respectively.With 1.5% ethyl cellulose alcoholic solution is binding agent, and said mixture is made soft material, it is crossed 16 mesh sieves again and makes wet granular.With 50 ℃ of aeration-dryings of above-mentioned wet granular, through 16 mesh sieve granulate, 80 mesh sieves sieve fine powder obtains the aspirin sustained release granule
3, with the caffeine granule, aspirin sustained release granule, the magnesium stearate mixing that obtain, be filled in the enteric capsule shell simultaneously.
Embodiment two:
With sucrose 1000 grams, maltose 500 grams, water 500 grams mix being heated with stirring to 120 ℃ gradually, continue to be stirred to main water evaporates then and finish, taking out this decocts thing 1000 gram and is put in second container, add and to be dissolved in the gram of 5 in 125 ml waters caffeine, 5 gram aspirin, it is heated with stirring to 150 ℃ gradually after, continue again to stir, water is evaporated.This is decocted thing pour in 3.3 milliliters of caked sugar moulds, be cooled to the lozenge that room temperature can obtain 4 grammes per square metres, every caked sugar contains 30 milligrams caffeine and 30 milligrams aspirin.
Embodiment three:
Caffeine and microcrystalline Cellulose with equivalent incremental method mixing, again with the pregelatinized Starch mix homogeneously, are added 5%PVPK30 solution and make soft material, sieve and granulate dry or directly granulate with one-step-granulating method.With aspirin, ethyl cellulose microcrystalline Cellulose, mix homogeneously after starch sieves respectively.Make soft material with 1.5% ethyl cellulose alcoholic solution, again it is crossed 16 mesh sieves and make wet granular.Dry.Again caffeine granule, carboxymethyl starch sodium and magnesium stearate are added mixing in the granule, tabletting, label Opadry coating solution coating.Get Film coated tablets.
Embodiment four:
(1) with the 100mg aspirin, 30mg caffeine, 52mg ethyl cellulose, 72mg microcrystalline Cellulose, 35mg starch are crossed mix homogeneously behind 80 mesh sieves respectively.
(2) be binding agent with 1.5% ethyl cellulose alcoholic solution, said mixture is made soft material, again it is crossed 16 mesh sieves and make wet granular.
(3) with above-mentioned wet granular in 50 ℃ of aeration-dryings, through 16 mesh sieve granulate, add the carboxymethyl starch sodium 13.5mg that crosses 80 mesh sieves, magnesium stearate 2.8mg, mix homogeneously, tabletting behind the 80 mesh sieves sieves fine powder.
Claims (9)
1, a kind of black/white preparation of Cure for insomnia comprises black preparation and white preparation, it is characterized in that: the prescription of black preparation is: 5-hydroxyryptophan: 50-300mg, and melatonin: 1-10mg, diphenhydramine or its acid-addition salts: 3-75mg,, VB
6: 0-10mg.The prescription of white preparation is: aspirin: 25-200mg, caffeine: 30-150mg.
2, black/white preparation according to claim 1 is characterized in that: the prescription of described black preparation is: 5-hydroxyryptophan: 100mg, melatonin: 3mg, diphenhydramine or its acid-addition salts: 25mg.
3, black/white preparation according to claim 1 is characterized in that: the prescription of described white preparation is: aspirin: 50mg, caffeine: 50mg.
4, black/white preparation according to claim 1 is characterized in that: the acid-addition salts of described diphenhydramine is selected from: diphhydramine hydrochloride, diphenhydramine citrate, diphenhydramine salicylate, tannin diphenhydramine, lauryl sulphate acid diphenhydramine or sulphuric acid diphenhydramine.
5, black/white preparation according to claim 1 is characterized in that: the acid-addition salts of described diphenhydramine is diphhydramine hydrochloride or diphenhydramine citrate.
6, black/white preparation according to claim 1 is characterized in that: described black preparation and white preparation dosage form are various medically acceptable various solids, semisolid dosage forms.
7, black/white preparation according to claim 1 is characterized in that: described solid dosage forms comprises: capsule, tablet, granule, powder, pill, granula subtilis, lozenge.
8, black/white preparation according to claim 1 is characterized in that: the white preparation of taking the minimizing hangover effect on black preparation, daytime of taking Cure for insomnia evening.
9, according to the purposes of the described black/white preparation of above-mentioned arbitrary claim 1 to 6 at medicine aspect preparation Cure for insomnia, adjustment sleep rhythm, the minimizing jet lag.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100934055A CN1299680C (en) | 2005-08-29 | 2005-08-29 | Black-white formulation for treating insomnia |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100934055A CN1299680C (en) | 2005-08-29 | 2005-08-29 | Black-white formulation for treating insomnia |
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| CN1299680C true CN1299680C (en) | 2007-02-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2005100934055A Expired - Fee Related CN1299680C (en) | 2005-08-29 | 2005-08-29 | Black-white formulation for treating insomnia |
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| WO2023106959A1 (en) * | 2021-12-10 | 2023-06-15 | ОБЩЕСТВО С ОГРАНИЧЕННОЙ ОТВЕТСТВЕННОСТЬЮ "НоваМедика" | Pharmaceutical composition containing melatonin and diphenhydramine or its pharmaceutically acceptable salt |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1352556A (en) * | 1999-05-27 | 2002-06-05 | 纽里姆药品(1991)有限公司 | Application of melatonin in the treatment of diseases |
| CN1646098A (en) * | 2002-04-08 | 2005-07-27 | 纽里姆药品(1991)有限公司 | Pharmaceutical formulation comprising melatonin |
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2005
- 2005-08-29 CN CNB2005100934055A patent/CN1299680C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1352556A (en) * | 1999-05-27 | 2002-06-05 | 纽里姆药品(1991)有限公司 | Application of melatonin in the treatment of diseases |
| CN1646098A (en) * | 2002-04-08 | 2005-07-27 | 纽里姆药品(1991)有限公司 | Pharmaceutical formulation comprising melatonin |
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