CN102973946A - Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases - Google Patents
Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases Download PDFInfo
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- CN102973946A CN102973946A CN2012103028194A CN201210302819A CN102973946A CN 102973946 A CN102973946 A CN 102973946A CN 2012103028194 A CN2012103028194 A CN 2012103028194A CN 201210302819 A CN201210302819 A CN 201210302819A CN 102973946 A CN102973946 A CN 102973946A
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Abstract
Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases
Description
The application is to be on July 19th, 2004 applying date, application number is 200480020770.7, and denomination of invention is divided an application for the application of " comprise by the liquid impermeable but gas can see through compositions and the purposes in treatment skin and other exocrine gland disease thereof of the coated component of layer ".
The present invention relates to the treatment of medical conditions, relate in particular at least part for the treatment of take eccrine obstruction or other malfunction as the medical conditions of feature, this exocrine gland especially refers to the exocrine gland conduit, refers specifically to sudoriferous duct.
Flourishing society is such as UK and USA in the west, and the probability that people suffer from many chronic diseases (such as essential hypertension, asthma, gastrointestinal tract inflammation) increases, although expensive medical intervention is arranged, the sickness rate of these diseases still continues to rise.
Known that in these chronic diseases some are relevant with eccrine pipe obstruction.The obstruction of sudoriferous duct and residual antiperspirant can cause milium as everyone knows, and it is exactly the acute inflammation dermatosis of knowing with miliaria.
The adult has 2 to 400 ten thousand sweat gland according to estimates, and these sweat glands have the conduit that leads to skin surface.Known antiperspirant is the fluid that mainly comprises water, also contains refuse, such as carbamide, sodium and other salt.
Milium appears when sweat duct gets clogged.Therefore antiperspirant can not arrive skin surface, and gets clogged in epithelium or corium, causes therein normal sensation of pricking with serious pruritus.Even when conduit got clogged, sweat gland still continues to discharge fluid and just below closed position, the pressure of antiperspirant makes catheter rupture, so that antiperspirant enters in the surrounding skin.If because emotion, heat or move former thereby antiperspirant is increased will be larger to the harm of surrounding skin then.
Dissimilar infringements can appear in the degree of depth according to described obstruction occurs.Cause having the miliaria alba of asymptomatic surface vesicles at the pipe obstruction of the epithelium the superiors, cause miliaria rubra and occur in epithelium than the depths and with the obstruction of inflammation, its take red lesion and pruritus appears and soft red grouper or pimple as feature.Such milium can be infected and be become pustule, and very disagreeable.Current treatment is included in cold environment kind and keeps several weeks, and the topical application lanoline grease, and it has temporary transient effect.
If pipe obstruction occurs in the corium upper surface, in being rich in the layer (pruritus layer) of teleneuron, the inflammation of aching not only but also itching will appear.This is unknown in the past milium type, identifies (called after milium 3 types) by the inventor, thinks that it causes the irritated dermatitis of atopy or eczema.
In dark and the most serious milium type, be called miliaria profunda, pipe obstruction occurs near the import that conduit enters dermal papilla, causes trickle asymptomatic, yellowish pink pimple.In miliaria profunda, perspiration is skin diffusion towards periphery, can't see and is not noted, makes capillary rupture on every side.The potential cause of the inventor thinks that Here it is essential hypertension because the capillary tube that more and more breaks causes the pressure in the blood circulation to raise, continues to raise with the age usually.The formation, particularly shank of the thrombosis that can initiation potential that breaks sometimes capillaceous.
To inadaptable heat but still keep people or those effort of high ambient temperature to make the people who oneself is in the high-temperature, may suffer from the acute miliaria profunda of large tracts of land.The Disability that the obstruction of a large amount of gland conduits makes health suitably lower the temperature by sweat evaporation may cause heat exhaustion or heatstroke.
Milium also can betide wears that airtight clothes people performs physical exercise or heat when exposing.This is the common reason that the polytype milium occurs, for example such as mining, fire-fighting, the occupation of messes and other muscle power work in thermal environment is provided.
People's skin of face is thin, only is skin of back thickness about 10%.The sudoriferous duct of skin of face blocks the skin milium that may cause any type, and the inventor finds that general type is the combination of miliaria rubra and milium 3 type (see above).This conjunction type milium is normally temporary transient, but may finally produce chronic erythema, blushes and have the pus kitchen of periodical attack and reddening of pimple.Finally, especially to the male, may cause special hamartoplasia and the phyma of disfigure, such as pachydermatosis, nose root hypertrophy.The inventor thinks that the combination of this milium type also can cause being characterized as the rosacea of red line, or telangiectasis, and described is its feature.Fatty external secretion pipe obstruction facial and other skin often causes the general disease with the acne vulgaris of rosacea.
In addition, the inventor finds that especially for the women, the obstruction of external secretion conduit may cause the vacuole that is full of perspiration in corium.If the affected area of skin is under pressure, the contact area when being seated such as thigh and buttocks, the conjunctive tissue of fatty tissue by the edge produces typical irregular indenture, the liparitosis of namely knowing in extruding corium.
The inventor finds that psoriasis disease may be one type of milium, and wherein owing to skin injury, infected by microbes sinks into below the perspiration pipe obstruction.
The inventor also recognizes, many Other diseases are subject to that in extracutaneous tissue excretory duct blocks or the impact of other malfunction.
The inventor thinks that the obstruction of head external secretion conduit may cause sanguimotor contraction or the interruption to brain, and itself can cause migraine.In addition, this chronic obstruction may cause polytype neurodegenerative diseases.
The inventor determines that the eccrine obstruction of lung mucomembranous surface causes asthma.The inventor thinks that also allergic rhinitis or Hay Fever are caused by the eccrine obstruction of the inner mucomembranous surface of nose.
Any eccrine obstruction may affect the skin of chest, and it obtains good supply by sweat gland and conduit.Equally, between whole adult age, women's chest has the fluid secretion activity to a certain degree from mammary gland, even when obviously not having lactogenic.The emulsus ejection also may be medicine or the hormone by the generation that can stimulate emulsion in addition, or the reason of stimulating nipple mechanically.The inventor thinks, breast duct is subject to the obstruction of external secretion perspiration conduit same way as and breaks, and this obstruction causes lump, cyst, pain and the tenderness of female chest.Therefore, the inventor believes that these diseases are subject to the impact of exocrine function.
Similarly, the inventor thinks that the obstruction of male prostate conduit causes its hypertrophy and compressing.
In addition, xerophthalmia conjunctivitis and glaucoma can cause by the obstruction of external secretion conduit, and the eccrine obstruction of gastrointestinal mucomembranous surface or malfunction be many inflammation diseases, comprises a reason of gastritis and colitis.In addition, the inventor finds this gastrointestinal tract inflammation, especially enteritis, may cause autoimmune response, autoimmune response may cause disease such as Crohn disease, rheumatic arthritis, osteoarthritis, systemic lupus erythematosus (sle), ankylosing spondylitis, multiple sclerosis, motor neuron disease, polycystic ovary syndrome, Bicuspid valve syndrome, type i diabetes, scleroderma, autoimmune thyroiditis, hyperthyroidism and many Other diseases.
The obstruction of lung and gastrointestinal external secretion pipeline or malfunction are thought the loss that relates to the mucomembranous surface natural immunity, infect thereby the patient is produced towards air or fluid.Therefore inventor's suggestion should be eliminated this situation that may be exposed to the people in the pathogen, such as the staff of patient and hospital, and begins to carry out before any medical procedure or medicine program, comprises vaccination.
Equally, especially to older people, they have large-area exocrine gland to block in the skin, lack the protection of antibacterial skin peptide, may cause intrinsic or general pathogen to be easy to enter by skin, may cause serious infection.
As everyone knows, type ii diabetes is relevant with the serum hyperglycemia with hypertension, and it is subject to the control of insulin hormone in addition usually.The inventor's argument is that insulin generation pancreatic duct works in the mode identical with the external secretion conduit.The insulin excessive secretion that being subject to hyperglycemia stimulates obtains modifying in the passage via conduit, and the insulin of so modifying is no longer valid, and Here it is " insulin resistant ", the reason of known type ii diabetes.
In addition, the inventor thinks that the excessive secretion of the hormone of stomach, intestinal, liver and pancreas causes these hormones partly to lose normal function, causes the control that loses appetite.Like this, any fat-reducing program to obesity can obtain assisting by comprising the treatment that hormone produces the external secretion conduit.
The treatment of other disease that the purpose of this invention is to provide milium and partly caused by obstruction or other malfunction of external secretion conduit.
The invention provides and be formulated as the sodium chloride that can not pass the epithelium barrier and block take exocrine gland or the purposes of other malfunction in the medicine of the medical conditions of feature in that the preparation treatment is at least part of.
In some embodiments, described sodium chloride can be crystalloid.
In some embodiments, described sodium chloride can be by forming the liquid impermeable but gas can see through the pack quilt of layer.
In some embodiments, described reagent can be ceramic, polymer or native paraffin.
In some embodiments, described reagent can be wrapped to form spheroid with sodium chloride.
In some embodiments, the diameter of described spheroid can be 1mm to 10mm.
In some embodiments, described spheroid can comprise the sodium chloride crystal that is coated with by by the Cera Flava of corn starch and Pulvis Talci sclerosis.
The present invention also provides by forming the liquid impermeable but gas can see through the sodium chloride of the pack quilt of layer.
In some embodiments, described reagent can be ceramic, polymer or native paraffin.
In some embodiments, described reagent can be wrapped to form spheroid with sodium chloride.
In some embodiments, the diameter of described spheroid can be 1mm to 10mm.
In some embodiments, described spheroid can comprise the sodium chloride crystal that is coated with by by the Cera Flava of corn starch and Pulvis Talci sclerosis.
The present invention also provide be suitable for treating at least part of take exocrine gland block or other malfunction as the medical conditions of feature and comprise sodium chloride and be fit to stick to paster on the skin.
In some embodiments, described paster can comprise the viscosity plaster that is fit to adhere on the skin.
In some embodiments, described paster can comprise hypoallergenic waterproof plaster.
In some embodiments, described paster is the shape of numeral 8.
In some embodiments, described paster can further comprise two sodium chloride spheroidal particle.
In some embodiments, described paster can further comprise above-mentioned any one sodium chloride through being coated with.
The present invention also provides a kind of device, and it comprises and is suitable for keeping holding device, the energy and by the actuator of driven by energy, being used for provisionally and discontinuously with the placed of described chemical compound against the patient of medical science active compound.
In some embodiments, described device is applicable to around the abdominal part that is worn on the patient or the chest.
In some embodiments, the described energy can be low tension battery.
In some embodiments, described device can further comprise an electronic timer.
In some embodiments, described actuator can be a spring return function push rod spiroid canal.
In some embodiments, described device is applicable to holding sodium chloride.
In some embodiments, described device is applicable to holding above-mentioned any one sodium chloride that was coated with.
The present invention also provides a kind of preparation as medicine, and it comprises medically active substance, described material by forming the liquid impermeable but the pack that gas can see through layer by or otherwise encapsulate.
In some embodiments, described reagent can be formulated as and make described material can not pass mammiferous epithelium barrier.
In some embodiments, described reagent can be formulated as and make described material can not pass mammiferous envelope barrier.
In some embodiments, described reagent can be formulated as and described material can not be passed enter in the mammiferous cell.
In some embodiments, the shape of described preparation can be selected from pill, tablet, lozenge, bolus, capsule, capsule sheet, granule, millimicro granule and microgranule.
In some embodiments, described preparation can be selected from suspension, emulsifiable paste and paste granular, millimicro is granular or microgranular.
In some embodiments, the preparation of described preparation can be used be used to keeping described preparation to approach or against patient's skin with paster.
In some embodiments, described preparation preparation can be used in the body of patients with implantation.
In some embodiments, the optional free ceramic of described preparation, polymer, native paraffin and a group of being formed by the Cera Flava of corn starch and Pulvis Talci sclerosis.
In some embodiments, one group of the optional free sodium chloride of described material, capsaicin, metformin, salicylic acid and salicylic derivant composition.
In some embodiments, one group of the optional free health endogenous substance of described material, food matter, vegetable material and ingredients.
In some embodiments, described preparation can with at least a preparation combination that is designed to be conveyed into the composition of solution.
In some embodiments, described preparation can with at least a preparation combination that is designed to be conveyed into the composition of solution for therapeutic purposes.
The present invention also provides a kind of preparation method of medicine, is included in to form the liquid impermeable but gas can see through coated in the reagent of layer or otherwise encapsulate the medical science active substance.
According to a first aspect of the invention, provide to be configured to the application of sodium chloride in drug manufacture that can not pass the epithelium barrier, this medicine is at least part of medical conditions take eccrine obstruction or other malfunction as feature for the treatment of.For example, may be obstruction or the malfunction of external secretion conduit.
Especially, this sodium chloride can be by forming the liquid impermeable but gas can to see through the reagent place of layer coated.In this aspect of the present invention and other side, described coated reagent can stop and passes medical science active substance of being wrapped in it or the coated path of therapeutic agent (such as sodium chloride).Can think that described being coated with is the parcel to sodium chloride (or other the coated material for describing in detail below).Like this, patient uses this medical science active substance (therapeutic agent that described sodium chloride or other describe in detail below is by described pack quilt or parcel) and can cause described sodium chloride (or other material that describes in detail below) without metabolism change, chemical modification or minimizing.
On every side coated of sodium chloride (such as sodium chloride crystal or granule) can be any liquid impermeable but the permeable barrier of gas, and it stops sodium chloride through entering when being absorbed (as) health or through reaching on the health.Described reagent can be ceramic (such as clay or Inorganic Non-metallic Materials), polymer or native paraffin.
As for sodium chloride, it can be wrapped to form spheroid, is 1 to 10mm such as diameter.For example: described spheroid can comprise that by the coated sodium chloride crystal of Cera Flava described Cera Flava is by corn starch and Pulvis Talci sclerosis.
Sodium chloride or general salt (chemical formula is NaCl) are in the natural existence in many places in the world, such as the mixing evaporant in Ore, rock salt and the salt lake.Qualitatively, sodium chloride contains 60.663% chlorine element (Cl) and 39.337% sodium element (Na).
Sodium chloride can be crystal habit, and sodium chloride crystal is cube structure, and is represented as the according to a first aspect of the invention preferred configuration of the sodium chloride that uses.
More preferably coated dose of parcel of sodium chloride.Described reagent can wrap up sodium chloride crystal, described coated impermeable liquid but can see through gas.The crystal that the present invention it is called such parcel is " zero consciousness treatment inertia reagent (Sensezero Therapeutic Inert Agent) ".
The sodium chloride crystal of parcel has represented key character of the present invention.Therefore, according to a second aspect of the invention, provide by forming the liquid impermeable but gas can see through the medically compounds effective of the pack quilt of layer, it is as medicine.
What should be appreciated that second aspect present invention coated can be applied to many medically useful chemical compounds, and most preferred compound is sodium chloride.
According to various aspects of the present invention, described coated can be for any liquid impermeable but the permeable barrier of gas, it stops described sodium chloride (or other material that describes in detail below) through entering health (when being absorbed) or through reaching on the health.Described reagent can be ceramic (such as clay or Inorganic Non-metallic Materials), polymer or native paraffin.Like this, sodium chloride crystal or granule can be coated with by Cera Flava, and described Cera Flava is by corn starch and Pulvis Talci sclerosis.
Although should be pointed out that sodium chloride is not the medically resultful material that it has been generally acknowledged that, to work as it and be applied in many aspects of the present invention, sodium chloride is medically effective.
In the preferred embodiment of second aspect present invention, sodium chloride is packed to spheroid, and its diameter is about 1 to 10mm, and preferred 3 to 8mm, more preferably 6mm.Described spheroid can comprise that by the coated sodium chloride crystal (it can be compressed) of Cera Flava described Cera Flava is by a small amount of corn starch and Pulvis Talci sclerosis.
Cera Flava by the sclerosis of a small amount of corn starch and Pulvis Talci is coated, with tablet of the prior art and with its analog be distinct, tablet of the prior art and its analog are coated with or wrap up (such as the wax polishing tablet) with wax.In the case, but wax is the water permeability, and is used for playing the effect that makes drug slow or delayed release, or for improvement of the medicament outward appearance.This has just formed contrast with the present invention, coated (even in the coated situation of wax-matrix) among the present invention be the water impermeable but gas is permeable.Cera Flava by corn starch and Pulvis Talci sclerosis has reached desired water impermeability.
Should be pointed out that the sodium chloride in the normal diet can not reach effect of the present invention, because this salt can be by sucking health above the gastrointestinal tract epithelium.Salt prepared in accordance with the present invention can this thing happens (as according to a second aspect of the present invention).
Following medical conditions is included in and can treats in the disease of (pre-defense sector or when symptom occurs) by using sodium chloride according to the present invention:
Miliaria alba, miliaria rubra, 3 type miliumes, degree of depth milium, chronic erythema, the reddening of periodical attack of blushing and having pustule and pimple, hamartoplasia, the phyma of disfigure, pachydermatosis, rosacea, telangiectasis, essential hypertension, migraine, neural degeneration, liparitosis (Cellulite), asthma, allergic rhinitis, Hay Fever, atopic eczema (Atopic eczema), chest masses and cyst, prostatic hyperplasia, the xerophthalmia conjunctivitis, glaucoma, gastrointestinal tract inflammation, gastritis, colitis, Crohn disease (Crohn), rheumatic arthritis, osteoarthritis, systemic lupus erythematosus (sle), ankylosing spondylitis, multiple sclerosis, motor neuron disease, polycystic ovary syndrome, the Bicuspid valve syndrome, type i diabetes, scleroderma, the autoimmune thyroiditis, graves, type ii diabetes, the hypertension relevant with type ii diabetes, acne vulgaris and obesity.
Here, refer to design to healing, alleviation, removal or the mitigation symptoms of any disorder of human body or animal body or malfunction by " treatment " or stop or reduce any treatment of infection potential.Term " treatment " also comprises treatment and human body or animal body maintenance or promotion optimum health or beautifying face such as dermatosis such as liparitosis (it is considered to improve looks, rather than body illness or malfunction).Similarly, " medically effective " material of mentioning here refers to the material that is used for the treatment of.Therefore, medically effectively material comprise and can be used for the treatment of disease or the material of prevention.
Above in the general treatement of described disease method for optimizing comprise use sodium chloride so that it approaches the exocrine gland conduit that blocks.The exact method that is appreciated that the preparation of sodium chloride and uses is determined by case disease to be treated.
It should also be understood that, the requirement of sodium chloride is determined by biologic activity and bioavailability, described biologic activity and bioavailability successively by method of application, be used for the physicochemical properties of the coated any reagent of salt are determined, no matter and sodium chloride be to use with independent treatment or combined therapy.Frequency of administration also will be subject to the impact of many factors, patient's especially to be treated health status.
Best application dosage can be decided by those skilled in the art, and will change according to concentration, method of application and the disease progression of specified disease to be treated, described preparation.The other factor that is determined by particular patient to be treated will cause needs to adjust dosage, comprise patient age, body weight, sex, diet and time of application.
According to the present invention, above-mentioned dissimilar milium or the treatment of Other diseases can comprise sodium chloride crystal near placed.
This can still preferably be avoided the direct method that contacts of described salt and skin to finish to skin the salt Binding by any.Preferred method comprises uses adhesive tape and Velcro velcro binder.Yet most preferred is to pass through paster with sodium chloride near the method for placed.This states paster can be that any type can make the sodium chloride crystal maintenance near the viscosity device of skin.People of the present invention claims this paster to be " zero consciousness treatment inertia paster (Sensezero Therapeutic Inert Patches) ".
This paster has shown key character of the present invention, and therefore provide a kind of paster in a third aspect of the present invention, this paster contains sodium chloride, be applicable to adhere on the skin, described patch is applicable to treat at least part of medical conditions take eccrine obstruction or other malfunction as feature.
In the preferred embodiment of the third aspect of the present invention, described paster can be the viscosity plaster that is suitable for sticking to any type on the skin, more preferably waterproof plaster, most preferably hypoallergenic waterproof plaster.Paster can be any shape, but is preferably the shape of numeral 8.
According to the most preferred embodiment of the third aspect of the present invention, the spheroidal particle of two pure sodium chlorides on described paster is provided, the spacing that preferred described sodium chloride particle separates remains on 1 to 1000mm, but most preferably described grain spacing remains on 30mm.The diameter of granule is preferably 1 to 10mm, but more preferably particle diameter is 2.5mm and has coated.Described coated preferred as second aspect present invention is described coated, and it comprises the water impermeable but the permeable material of gas, described material prevents that sodium chloride from transmitting and passes skin.
Another is operative installations with sodium chloride crystal near the preferred version of placed, and described device is placed sodium chloride crystal with therapeutic purposes against skin (against skin) provisionally and discontinuously.The inventor is called " zero consciousness therapy equipment (Sensezero Therapeutic Device) "
This device has shown a key character of the present invention, and therefore provide a kind of device in a fourth aspect of the present invention, comprise and be suitable for holding holding device, the energy and by the actuator of driven by energy, being used for temporarily and discontinuously with the placed of described chemical compound against the patient of medical science active compound.Described device can be used for treating at least part of disease that is caused by exocrine gland obstruction or other dysfunction.
According to a forth aspect of the invention, this device can for by the miniature locking device of any material manufacture, preferably be made of plastics.Described device can be worn over the patient Anywhere, but more preferably at patient's abdominal part or chest.In the enclosure energy source can be arranged, such as low tension battery, also have electronic timer.Actuator can be spring return function push rod spiroid canal (spring return push-rod solenoid).Described device goes for holding sodium chloride.Preferred pure sodium chloride crystal places the described device of holding.Sodium chloride can be coated with according to the coated of second aspect present invention.This coated sodium chloride is that water impermeable but gas can see through, and can prevent that therefore the salt transmission from passing skin.
Daily dose can provide to use separately.Selectively, used sodium chloride can require in one day perhaps repeatedly to use for twice.For example, can use over many days by wearing continuously described device according to sodium chloride of the present invention, and require described device in per hour, to be activated a few minutes.As selection, the patient can adopt a paster that comprises daily dosage, and paster was reapposed over the diverse location of skin after per 24 hours.
The obstruction of excretory duct or the disease that other malfunction is feature can be treated by any one method that first, second, third, fourth aspect of the present invention comprises beyond at least part of.For example, the paster according to the third aspect of the present invention can be used for abdominal part.
According to the present invention, can comprise sodium chloride crystal near placed the obstruction of dissimilar miliumes or other at least part of in addition excretory duct or the treatment of the disease that malfunction is feature.All diseases (skin and non-skin) treatment that can use the same method (as using the paster according to third aspect present invention at skin, or as selecting, using the device according to fourth aspect present invention).Can strengthen or strengthen treatment by using simultaneously according to the coated chemical compound of the warp of second aspect of the present invention, it also can be treated separately.
Dermatosis on face, lower limb or arm can be treated according to the device of fourth aspect present invention by paster or the placement of the third part according to the present invention at abdominal part or chest placement, if possible is placed on the not infected skin.Preferably also use in addition as a rule the chemical compound coated according to the warp of second aspect present invention.The treatment that can use the same method of non-dermatosis.Some therapists may wish to use the paster according to third part of the present invention, or according to the device of fourth aspect present invention, or according to the coated chemical compound of the warp of second aspect of the present invention as monotherapy.After the disease treatment success, a kind of preventive drug that can be used as in above-mentioned three kinds of methods is regularly used.
But, preferably by with the sodium chloride according to the second aspect present invention form of Definition, with oral or alternate manner, introduce health, the treatment of any disease is strengthened synergistically.
Be appreciated that the present invention's (at it aspect all) is particularly useful to the treatment patient.Yet the patient can be other mammal that any veterinary is concerned about.
Although the inventor does not wish to be fettered by any hypothesis, what can believe is, sodium chloride can be used at least part of obstruction take the external secretion conduit that caused by following reason or other malfunction and is the treatment of the medical conditions of feature.
The inventor has considered the behavior the social modern of prosperity, and find that the transformation from habitual (original genetic habituation) (i.e. the human behavior natural environment) of original heredity to bad habit (adverse habituation) (being people's non-natural or modern environment) can cause many health problems, comprises milium and those diseases above-mentioned.Think that this transformation can show exocrine gland, and particularly in physiology's change of sweat gland.
The inventor thinks, normal sweat gland or in foundation level or in the higher level perspire.The dual state of this sweat gland is considered to naturalness, and the inventor is habitual with the original heredity of this state called after sweat gland.
In this naturalness, all sweat glands continue to produce perspiration in foundation level.Usually cumulative exercise or be exposed to and pine for causing increasing sweat gland to become in higher level work.Regular firmly to temper or be exposed to the described hereditary custom state of pining for keeping the antiperspirant conduit be necessary, because they can cause a large amount of of perspiration to be flowed, it causes cleaning conduit because physics of rapid flow fluid promotes.
Be not regular exercise the people, run into such as the people of the emotion of pressure and live in the repeated events that the people's experience perspiration slightly higher than foundation level in artificial and weather gentleness discharged.Therefore the inventor thinks that the result is fixed on a slightly high level by the resorbent sodium of conduit, makes this conduit remain on the bad habit sexual state, even the stimulation of perspiration is stopped.The state of this acquisition makes the patient easily suffer from the disorder relevant with the obstruction of sweat gland, is lower than by the level of antibacterial peptide with the required effective skin care of antimicrobial pathogen because the salinity in the perspiration drops to.This just makes microorganism can enter conduit, so it is blocked by consequential immunoreation.
In the initial period that may treat research of above-mentioned medical conditions, the inventor has considered the unicellular prokaryote in ocean in initial evolution epoch existence.The same with modern cell, these prokaryotic cell active transpories advance or transport out sodium to keep the low sodium of internal medium.Because anyly comprise the impact that the health of the water of dissolving salt is subject to concentration change, natural flow and lamination are being followed in the back, and the inventor reaches a conclusion, in order to survive, prokaryote the earliest must be able to detect the composition of the molecule of inside and outside dissolving, and reacts according to information.People of the present invention claims this power of test to be " zero consciousness (sensezero) ".
So the inventor has drawn the human body that is surrounded by fluid, the fluid with gaseous state is arranged, i.e. air, the skin of contact and lung, and the gastrointestinal tract that contacts with liquid.The inventor reaches a conclusion, if the existence of the superfluous sodium of somatosensory in described gas and the liquid environment, it is habitual that the exocrine gland that is in bad habit can freely reset to heredity.
Therefore, according to the present invention, the basis for the treatment of and prevention milium and disease above-mentioned is to providing the sodium amount in the air of health and the liquid environment, and it is superfluous habitual to allow to reset to heredity that it shows as indication.In addition, in order to prevent health sodium chloride is reduced weakening gradually of sensitivity and therapeutic effect, the inventor finds, must become to make health can feel new other sodium salt with referral prevention and do not absorb it.Therefore, salt used according to the invention should be prepared into and can not pass the epithelium barrier.
Everybody knows that also in multicellular animals, complicated cell signal transmission system is used for movable as existence and apoptosis, and these effect of signals or healthy maintenance and the advancing of disease of control.
The inventor also points out, many for enter medicine that the health circulation prepares in fact in health not by metabolism, be that existence by them has reached its therapeutic effect but show as, and then excrete steadily.
Therefore the inventor reaches a conclusion, and many medicines can be by the existence in physical environment but do not entered circulation and have therapeutic effect.He thinks that physical environment is fluid.In the situation of skin and lung, fluid is gas, i.e. air; In the gastrointestinal situation, fluid is liquid.
The inventor does not wish to be fettered by any hypothesis, but think medicine in physical environment rather than the health circulation in existence affect signal transmission and zero consciousness (sensezero) of cell, and may so when medicine is not in circulation, have the therapeutic effect of expectation.
Thereby except applicable to the sodium chloride, top conclusion and each aspect above the present invention are also applicable to the medicament that is combined with the material except sodium chloride, paster and device.Especially, the sodium chloride in the above-mentioned aspect of the present invention can be replaced by capsaicin (capsaicin), metformin, salicylic acid or salicylic derivant.In addition, sodium chloride can be substituted by health (such as suitable human body or animal body, depending on the intended recipient of any Drug therapy or treatment) endogenous substance, food or medicine.
Present very many manufactured purposes that is used for the treatment of of chemical compound.Naturally occurring material is such as vegetable material, also for the preparation of therapeutic purposes.For this purpose, these chemical compounds and material are called " medicine ".
Medicine is almost always to the chemical compound of health heterogeneous (foreign).Similarly, different from endogenous substance, they are not constantly to be formed and to eliminate.Therefore absorption, bioavailability, distribution and the elimination of medicine have determined initial, persistent period and the intensity of effect of drugs.
Drug absorption in mammalian body is decided by their physicochemical properties, their preparation and route of administration.The actual dose form (such as tablet, capsule, solution) that comprises medicine and suitable vehicle can be mixed with preparation and use by different approaches, and that described approach comprises is oral, buccal (buccal), Sublingual, rectum, non-intestinal, skin and suction.The prerequisite that absorbs is medicine dissolution.For example solid pharmaceutical products such as tablet decompose and depolymerization fast or lentamente, may occur after medicine enters solution but only absorb.
Medicine is designed to enter systemic circulation to play expected effect.Therefore the technical staff of those field of pharmaceutical preparations is concerned about effective transmission, control transmission time, decomposition and the absorption that obtains by biological barrier and makes the bioavailability maximization in circulation and aspect the therapeutic goal.Some medicines pass cell membrane and enter in the cell self.
Medicine in circulation also can wide region chemical reaction metabolism in health, described chemical reaction comprises in oxidation, reduction, hydrolysis, hydration, conjugation, condensation and the isomerization, and these reactions must carefully be predicted.Do not wish that the metabolite that obtains may be difficult to eliminate in health.May harmful interaction occur with other medicines or endogenous substance also.
Medicine in the circulation can along with the time in tissue or health lacuna accumulation, thereby and cause the result who does not expect.Medicine in the circulation can penetrate its zone that may be harmful to, as passes blood-brain barrier or Placenta Hominis.
Therefore, in the preparation of medicine and test, need very high technical ability, and when the preparation cost of prodrug very high, often be several hundred million sterlings.But, nearly all medicine has the side effect of not expecting in circulation, and may be harmful to user.Although government organs have formulated very hard and fast rule, surpass 100,000 death owing to the untoward reaction through the approval medicine in that the U.S. is annual.
Therefore, according to a fifth aspect of the invention, provide a kind of preparation as medicinal application, said preparation comprises by forming the liquid impermeable but gas can be through the pack quilt of layer or the medically effective material that otherwise encapsulates.
The inventor is called " ActivSignal " (TM) class medicine.
Described reagent can be configured to described material can not pass mammiferous epithelium barrier.Described reagent can be configured to described material can not pass mammiferous envelope barrier.Described reagent can be configured to described material and can not pass and enter in the mammiferous cell.
Medically effectively material can be selected from sodium chloride, capsaicin, metformin, salicylic acid and salicylic derivant.It can be selected from health endogenous substance, food and medicine.
Preparation can be prepared by several different methods, comprise for mouth, that contain, nose, the Sublingual, rectum, parenteral, local, skin with suck using and using.Described formulation forms comprises nanoparticle (nanoparticle) shape and microgranule (microparticle) shape.
For example, described preparation can be pill, tablet, lozenge, bolus, capsule, capsule sheet, granule, nanoparticle or particulate form.It may be granular, the nanoparticle or microgranular such as suspended substance, emulsifiable paste or paste.
Described the 5th aspect of the present invention provides to be had therapeutic effect and not to have medicine to enter the medicine of the adverse side effect of circulation, the overdose that described side effect such as accumulation, toxicity or patient are possible.Described medicine of the present invention has consistent therapeutic effect, because " dosage " is constant, and does not have the variation of metabolism or the metabolism by product.The present invention can be by discharging dampness to improve the medicine storage life-span.In the present invention, some health endogenous substances can be used to therapeutical effect, because do not enter circulation after these material preparations, these materials are not effect in circulation.
According to claim 26, each preparation-29 be prepared as and use paster to keep described preparation to approach or against patient's skin.
Described preparation can implanted patient body in.
Described reagent can be for ceramic, polymer, native paraffin or by the Cera Flava of corn starch and Pulvis Talci sclerosis.
Described material can be sodium chloride, capsaicin, metformin, salicylic acid or salicylic derivant.
Described material can be the endogenous substance in the health, food matter, vegetable material or medicine.
This preparation can combine with at least a preparation that is designed to be sent to the composition in the solution, especially is combined with at least a preparation that is designed to be sent to the composition in the solution for therapeutic purposes.
In one embodiment, described active component is configured to oral tablet with the natural Cera Flava of excipient, corn starch and Pulvis Talci.This preparation method is known for those skilled in the art.In whole pharmaceuticals industry, because low production cost and be easy to process wax-matrix and be widely used in medicine and transmit.In the medicine transmission sheet goods of routine, the ratio of excipient is about 1% to 5% by weight in the tablet, and be designed to make active component easily at once or delayed release in solution.In its most preferred embodiment, described excipient, a large amount of wax adds a small amount of corn starch and Pulvis Talci, part by weight is 20% to 45% in tablet mixture.This new preparation method is not to be designed to discharge any active component in liquid solution, but wax-matrix innately has gas-premeable.
In more preferred, the active component of tablet is by polymer encapsulated (enclose), and is configured to the liquid impermeable but gas can see through.In preferred embodiments, active component can be encapsulated by ceramic, and is configured to the liquid impermeable but gas can see through.In the 4th embodiment, active component can be encapsulated in metal tablet or the capsule, such as the rustless steel of perforation, allow gas by but do not allow liquid to pass through.Other embodiment comprises pill, lozenge, bolus, capsule, capsule sheet, granule or any suitable product type, size or shape, the taking of any approach, and the protected in case contact liq of active component wherein, but it may contact gas.
The integrity of the liquid impermeability feature of expectation test formulation, and its physical integrity that in use keeps.For example, the testing in vitro that tablet is suitable is, stirs 3 hours in its pH being adjusted into 3 water with hydrochloric acid; Then, continue in pH being adjusted into 7 water with sodium bicarbonate, to stir 24 hours.Can be without any the change of obvious degree by this test drug.
In vivo, oral after, tablet can be by retrieving test from excremental, and it can find not change through behind the health, or only have the change of insignificant degree.
The medicine of preparation can be formulated as nanoparticle or particle size according to the present invention.US Patent No. 4622244 discloses active microcapsule, it is by the microcapsule of suitable polymer production size less than 300 microns, namely be fit to the suspension media by little pin injection commonly used in medical practice, thereby obtain active substance is controllable or sustained being discharged in the health circulation.This production method is known for a person skilled in the art, and in example of the present invention, by with the liquid impermeable but production is finished in the encapsulation of the permeable wax of gas or polymer or other suitable barrier.
Any embodiment can be allocated easily for treatment or combination are used for multiple treatment separately.Any embodiment can comprise easily above a kind of active component.Any embodiment can be easily and the preparation combination that is prepared as at once or postpones or selectively be transferred to any other active component in the solution.
Because therapeutic effect of the present invention is determined by the existence of this medicine in physical environment, can make arrangements to prevent along with the esensitization of time or weakening gradually of therapeutic effect.In oral situation, esensitization continues mobile avoiding by medicine at gastrointestinal.In situation about using by other approach, may need to provide discontinuously and regain medicine of the present invention, for example in per 30 minutes, provide 3 minutes, to avoid the generation of esensitization.For example, the tablet of ActivSignal class medicine can be by using a device to be placed on discontinuously on the skin and regaining, and described device comprises the actuator of electronics or other energy drives, remains near the patient skin.Can make to use the same method, wherein be preferably used in that surgery is used or other side is implanted ActivSignal class medicine in patient body.As selection, very small amount of described preparation can use at long interval.For example transdermal patches can provide according to the present invention two medicines (described medically active substance) granule of preparation, and diameter is 2 to 3mm, spaced apart about 30mm placement, and described paster for example is being moved on the diverse location of skin after per 12 hours.
A kind of preparation method of medicine also is provided according to a sixth aspect of the invention, and described method is included in and forms the liquid impermeable and gas can see through coated in the reagent of layer or encapsulation effective material medically otherwise.
The different characteristic of other side of the present invention discussed above is applied in a sixth aspect of the present invention equally.
Be appreciated that, the amount of medicine used according to the invention and any impact that will be subject to route of administration for physicochemical properties coated or that otherwise encapsulate the reagent of described medicine, also be subject to other and permitted multifactorial impact, described factor comprises patient's to be treated health status.
By following description and with reference to some figures in the following accompanying drawing, the present invention will be more obvious, and only by embodiment, described figure has shown form of the present invention, and described figure is:
Fig. 1 has illustrated paster according to a third aspect of the invention we.
Fig. 2 has illustrated the device of fourth aspect according to the present invention; With
Fig. 3 has illustrated the profile of the device of fourth aspect according to the present invention.
Among Fig. 1, " A " illustrated the paster of the third aspect according to the present invention, shown that its front bonding agent is coated with side, it is the hypoallergenic waterproof plaster of the spheroidal particle of 2.5mm by the diameter with the coated sodium chloride of two warps, the about 30mm of the spacing of described two spheroidal particle, and be fixed on the binding agent of described plaster; " B " illustrated the reverse side of identical hypoallergenic waterproof plaster; " C " illustrated the side view of hypoallergenic waterproof plaster, shown the spheroidal particle through two 2.5mm of coated sodium chloride, the about 30mm in the interval of described spheroidal particle, and be fixed on the binding agent of described plaster.
Fig. 2 and Fig. 3 have illustrated the device according to fourth aspect of the present invention.Scale is about 3 to 1.These picture specifications the coated sodium chloride block (1) of about 12mm x 13mm x 4mm; Spring return function push rod spiroid canal (2); Low tension battery (3); Electronic timer (4); The handle (5) of belt or rubber plaster is installed; Be used for the cabinet (6) of described device against placed.
Embodiment
Embodiment 1
Background
Fructus Capsici powder (Cayenne pepper), a kind of common composition of food, it extracts from Fructus Capsici (chilli pepper) (Fructus Capsici (Capsicum annum)) seed pod shell.The active component of Fructus Capsici is the plant alkaloid capsaicin.The emulsifiable paste or the lotion that contain the 0.025-0.075% capsaicin have sale in market, and the application in the dermatological for the treatment of pruritus and pain has very long history.In the time of on being applied in skin, capsaicin cause with from the relevant burning sensation of the depletion of the neuropeptide of nociceptor teleneuron.There is report that a large amount of pruritus dermatosiss (denmatoses) have successfully been suppressed pruritus (people such as Reimann S, " local application capsaicin treatment pruritus and pain in dermatological " Hautarzt.2000Mar by local application; 51 (3): 164-72; PMID:10789077).
Bleb (blistering) and hemorrhage appears sending out in the dermatosis of atopic eczema (dermatitis) for itching very much when this disease has inflammation speckle, liquid body exudate, scratching.Many patients upset sleep because continue pruritus.The opening of inflammation (open nature) refers to can not be used for alleviating the eczema pruritus with the local capsaicin of burning sensation.In fact local capsaicin can cause dermatitis.
Method
The Fructus Capsici powder spherical pill of and compressed formation diameter 7mm coated by the Cera Flava preparation of a small amount of corn starch and Pulvis Talci sclerosis.According to the present invention, these are to be prepared into gas can see through and the ActivSignal class medicine of liquid impermeable.The pill sample stirred 4 hours in external acid water, and stirred 24 hours in alkaline water.It is complete that pill still keeps, and do not find capsaicin in water.
Recruited six adults that suffer from atopic eczema (dermatitis), its main suit's pruritus, and it is using separately topical formulations with mitigation symptoms.Obtaining patient's informed consent postscript, everyone requires in the afternoon take a described Fructus Capsici ActivSignal class pill at 3, and thereafter until 8 of the next mornings just can use its topical remedy to process.Everyone required in an identical manner continued treatment 7 days, and everyone is in subsequently the situation that alleviates from the pruritus in eve of assessing them every day by phone.4 patient report the result of ActivSignal class Drug therapy, 100% mitigation symptoms in everyone 7 nights.As the result of ActivSignal class Drug therapy, 1 patient report 90% mitigation symptoms, 1 patient report 50% mitigation symptoms.There is not the report of adverse side effect.Felt to warm in the 2-3 of patient report after taking first described pill hour and slight perspiration for 2.
Can reach a conclusion, can see through and the Fructus Capsici powder preparation of liquid impermeable is effective to treatment eczema pruritus according to gas of the present invention, not have the report of adverse side effect.
Embodiment 2
Background
Metformin, biguanide to the treatment of type ii diabetes (diabetes mellitus), has been used nearly 8 years in the U.S., has surpassed 20 years in Europe.In this period, it has become the oral hyperglycemia preparation of writing out a prescription the most widely.Its mechanism of action comprises the basic generation of passing through the endogenous glucose of supression of liver.Whether medicine in muscle and fat, really has the insulin sensitivity effect in peripheral organization, still has some arguements.Even so, because use the metformin insulin level to descend, it is called as " insulin sensitivity agent ".Metformin has also shown to have some useful effects in cardiovascular risk factors, and it is unique oral antihyperglycemic agents, and the large artery trunks amount that therefore reduces with diabetic is extremely relevant.Cardiovascular disease, impaired glucose tolerance and polycystic ovary syndrome are considered to the complication of insuline resistance syndrome now, and with metformin be used for these especially the interest of common disease of metabolism constantly increase.Yet diet and temper the basis be still the treatment insulin resistant, the pharmacological intervention by using metformin now are alternative method of extensive use.
Yet metformin is considered to sometimes accumulate in human body, has therefore increased the risk of lactic acidosis, and it is potential fatal disease.Therefore think that metformin should be forbidden in many Chronic hypoxia blood disorders diseases, Chronic hypoxia blood disorders disease may be relevant with lactic acidosis, such as cardiovascular, kidney, liver and disease pulmonary, and age growth.
Method
The 250mg metformin is by being formed the spherical pill that diameter is about 7mm by the Cera Flava preparation of a small amount of corn starch and Pulvis Talci sclerosis is coated and compressed.According to the present invention, these are prepared to gas and can see through and the ActivSignal class medicine of liquid impermeable.The pill sample stirred 4 hours in external acid water, and stirred 24 hours in alkaline water.It is complete that described pill still keeps.Not finding by analysis has liquid to enter the pill sample.
5 adults that suffer from separately by the type ii diabetes of metformin control have been recruited.Before the beginning Or Metformin In Treating, by fasting glucose (FPG) diagnosis, this group's fasting glucose is 10 to 15mmol/l.General dosage range is from twice of 500mg metformin every day to 850mg metformin every day three times.5 people's FPG is controlled in below the 8nmol/l, and the value of measuring weekly is 5 to 8mmol/l.3 adults among 5 adults that recruit have metallic taste (metallic taste) once in a while in mouth, and 5 all adult's reports have abdominal discomfort once in a while, for taking the side effect of metformin.
In Informed Consent Form, 5 adults agree to replace conventional metformin with the ActivSignal metformin, and its replacement ratio is each conventional metformin tablet that an ActivSignal metformin pill replaces them usually to take, and the time was 4 weeks.
In described 4 weeks test, when taking described ActivSignal metformin, all 5 their FPG of adult's report are controlled to below the 8mmol/l.The report of being free from side effects.
Can reach a conclusion, ActivSignal metformin according to the present invention has with the metformin of routine medium-sized type ii diabetes people identical therapeutic effect is arranged, but the ActivSignal metformin reduces or is free from side effects.In addition, because the ActivSignal metformin is not released in the health, just may not accumulate in the health, so the ActivSignal metformin may can be used in treatment and the patient's of the relevant chronic disease of lactic acidosis general taboo situation.
Embodiment 3
Background
Aspirin is salicylic acetyl derivative, and it is used for bringing down a fever, ease the pain, reducing inflammation and make blood thinning.Usually the disease with aspirin for treatment comprises headache, muscle and arthralgia and the inflammation that is caused by rheumatic fever and arthritis.Aspirin thinks that antagonism upsets the synthetic heating that causes, pain and the inflammation of specific prostaglandin in the health.Restrain the ability that blood clotting forms because it has, can also prevent with the aspirin of low dosage heart attack and apoplexy, and the control unstable angina pectoris.The hypertension (toxemia) of the danger that this medicine is used for some cancer of prevention, occur sometimes in conceived process and migraine are also in investigation.
Normal dosage may cause nausea, vomits, diarrhoea or gastrointestinal hemorrhage.Large dosage causes Acid-Base imbalance and disordered breathing, and may be fatal, especially to the child.The development (combination that the fatty of acute encephalopathy and internal organs infiltrates) that aspirin also has been used for the treatment of the Reye syndrome (Reyes Syndrome) among the child of viral infection with Aspirin interrelates.Acetaminophen (acetaminophen) but can not cause gastric irritation, low grade fever and ease the pain and do not reduce inflammation, usually replace aspirin.Ibuprofen can be used for replacing aspirin to reach 10 days and need not seeking advice to the doctor.Ibuprofen may have the side effect similar to aspirin, although it is uncommon.
Trace back to 19 end of the centurys salicylic acid or 2-oxybenzene formic acid C
6H
4(OH) CO
2H is colourless, lenticular organic carboxyl acid, and it is used as the oral pain alleviating agent, until than the acetyl derivative of low irritant, the invention of aspirin.Other salicyclic acid derivatives is used to the active component of many topical formulations, and described preparation comprises sunscreen cream (sun creams), toothpaste, antiseptic and food.The application of aspirin in global medicine is very extensive, and just just sell 80,000,000,000 dosage in the U.S. every year, and aspirin is the active component that surpasses 50 kinds of over-the-counter drugs (over-the-counter).
Method
The pharmaceutically grade aspirin is hydrolyzed into salicylic acid, then uses by the Cera Flava of corn starch and Pulvis Talci sclerosis to be coated with, and is compressed into the pill of diameter 6mm.According to the present invention, these are made into gas and can see through but the ActivSignal class medicine of liquid impermeable.The pill sample was stirred 4 hours in external acid water, then stirred 24 hours in alkaline water, and it is complete that the sample of described pill still keeps, and do not find that by analysis liquid enters described sample pill.
Recruit 12 adult's quantity-unlimiting ground Aspirins or acetaminophen (acetaminophen) or ibuprofen and alleviated the arthralgia of moderate with appropriateness, be up to maximum recommended dosage every day, be 12x aspirin 300mg, or the ibuprofen 200mg of 8x acetaminophen 500mg or 6x.Some Aspirin in the group and the combination of acetaminophen are up to combined recommendation dosage every day.
According to Informed Consent Form, the group member agrees to replace 3 weeks of its conventional analgesic with ActivSignal salicylic acid pill.Inform that they begin to take 1 ActivSignal salicylic acid pill every day when requiring, if or need to take 2 (1 of morning, 1 of evening).Need to take 6 pills (each 1) every day if inform them, the minimum interval of taking is 2 hours.When off-test, 6 individual reports ActivSignal salicylic acid pills have the more effective effect that eases the pain than their conventional analgesic.Further 5 individual reports ActivSignal salicylic acid pills have the identical level that eases the pain with their conventional analgesic.These 11 people's most of times are taken 1,2 or 3 ActivSignal salicylic acid pill every day.Find that nobody need to take above 3 described pills in arbitrary sky.Everyone report is taken ActivSignal salicylic acid pill and is seemed that analgesic than their routine lasting time that eases the pain is longer.The report of being free from side effects.The effect that 1 people finds ActivSignal salicylic acid pill is lower than her the usual ibuprofen of taking, and has withdrawed from test.
Can reach a conclusion, ActivSignal salicylic acid pill according to the present invention be free from side effects report, effectively, the analgesic of longer duration.
Embodiment 4
Background
Essential hypertension is one of main health problem of flourishing society, and it has affected and has surpassed 20% adult population.Essential hypertension is defined as the lasting high pressure of unknown cause.Untreated essential hypertension can cause heart attack (myocardial infarction), congestive heart failure and other heart damage, arteriosclerosis, kidney damage, apoplexy and blind.
Inventor's discovery causes that the main cause of essential hypertension is the popular of asymptomatic miliaria profunda in the flourishing social population, and this disease causes inflammation, and inflammation causes that the pressure in the skin capillary tube raises.Milium is the result of excessive maintenance sodium in the sudoriferous duct.Comprise subsequently the ActivSignal class medicine of sodium by use, this excessive maintenance may be reversed, and can prevent milium and essential hypertension thus.
Adult's Blood Pressure Classification of World Health Organization (WHO) and international hypertension association (International Society of Hypertension) (revision in 1999) is listed in table 1.
Table 1
| Classification | Systolic pressure | Diastole is pressed | |
| Best | ＜120 | With | ＜80 |
| Normally | ＜130 | With | ＜85 |
| The high value of normal arterial pressure | 130-139 | Or | 85-89 |
| Mild hypertension | 140-159 | Or | 90-99 |
| Moderate hypertension | 160-179 | Or | 100-109 |
| Severe hypertension | ＞180 | Or | ＞110 |
[0184]All values are mmHg.Patient measures during sitting posture.
Sodium chloride or general salt is in the many local naturally existence in the world, and qualitatively, sodium chloride contains 60.663% chlorine element and 39.337% sodium element.Sodium chloride crystal is cubic shaped, and can be used as pure chemicals use.
Sodium chloride is the endogenous substance of mammalian body, and the basis for sustaining life, but the chemicals of daily picked-up does not find to have therapeutic effect.In fact recommend Essential Hypertensive Patients is carried out the restriction of sodium chloride.
Method
Pure sodium chloride is by coated by the Cera Flava of corn starch and Pulvis Talci sclerosis and be compressed into the granule of the ActivSignal class medicine of the pill of ActivSignal class medicine of diameter 6mm and diameter 2mm.Per two described granules are fixed on the former paster of adhesive low strain, the about 30mm of distance.
After the informed consent, 9 patients that suffer from slight, moderate or severe hypertension are required to participate in test.Before beginning test, taked the stationary holder appearance to test everyone blood pressure after 15 minutes described patient.After ensuing 10 minutes, test again described patient's blood pressure, and record the meansigma methods of reading of twice systolic pressure and the meansigma methods of twice diastolic pressure.Test is to adopt Omron 705IT sphygomanometer, a kind of clinical effective instrument.Available little, in, large cuff, and select according to the description of production firm.
Then require patient fixedly to contain the paster of two ActivSignal class drug particles at any position of its preabdomen.Then, in 3 days of following after per 24 hours new paster be fixed on different positions and old paster is dropped.Also allow patient take the pill of a kind of ActivSignal class medicine at first and the 3rd day mouth of a river with about 200ml of test.
The test the 1st, 2,4 with 6 days after test blood pressure according to identical mode respectively.
When on-test, 4 among the patient is mild hypertension, and 3 is that moderate hypertension and 2 are severe hypertension.After 4 days, the blood pressure measurement of listing in table 2 shows treatment after-contraction drops 27%, and diastolic pressure descends 18%.
After 4 days, at this moment in " the best " classification, 2 patients' blood pressure is at this moment in " normally " classification for 6 patients' blood pressure.Originally at this moment a patient who suffered from severe hypertension is classified as and suffers from mild hypertension.After 6 days, as shown in table 2, after treatment stopped, the beneficial effect for the treatment of still continued.
These data declarations, use as can be easily according to the sodium chloride of ActivSignal class medicine of the present invention, rapidly with Blood pressure drop within normal range, so patient no longer is considered to the hyperpietic.Treat to have capillary of skin is returned to its naturally effect of free-pouring function.
The present invention has and blood pressure is returned to it is considered to be normal effect.Therefore as everybody knows, essential hypertension is chronic progress disease, and can expect, when treatment can repeat, after treatment some months or in several years patient can not suffer from again hypertension.
Current drug products may need to take medicine all the life, has disagreeable side effect, and it can not treat potential disease (underlying disease), compare with the treatment of using this medicine, the present invention is quicker, more effective and treatment cost is lower to the treatment of essential hypertension, and does not have known side effect.
The results are shown in Table 2.
Table 2
Claims (6)
1. compositions, comprise at least a material by the pack quilt, wherein said reagent forms around described material and prevents the described coated liquid impermeable of described material permeance but gas can see through layer, wherein said material is selected from the group that is comprised of sodium chloride, capsaicin, metformin, salicylic acid and salicylic derivant, and described reagent is the Cera Flava by corn starch and Pulvis Talci sclerosis.
2. compositions according to claim 1, wherein said material comprises sodium chloride.
3. compositions according to claim 2, wherein said sodium chloride is crystalloid.
4. compositions according to claim 3, wherein said reagent parcel sodium chloride forms spheroid.
5. compositions according to claim 4, the diameter of wherein said spheroid is 1mm to 10mm.
6. according to claim 4 or 5 described compositionss, wherein said spheroid comprises the coated sodium chloride crystal of Cera Flava by corn starch and Pulvis Talci sclerosis.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0316940.6 | 2003-07-19 | ||
| GB0316940A GB0316940D0 (en) | 2003-07-19 | 2003-07-19 | Treatment of skin and other medical conditions |
| GB0327006.3 | 2003-11-20 | ||
| GB0327006A GB0327006D0 (en) | 2003-07-19 | 2003-11-20 | Drug compositon and therapeutics |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480020770 Division CN1826102A (en) | 2003-07-19 | 2004-07-19 | Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102973946A true CN102973946A (en) | 2013-03-20 |
| CN102973946B CN102973946B (en) | 2015-03-18 |
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| CN 200480020770 Pending CN1826102A (en) | 2003-07-19 | 2004-07-19 | Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases |
| CN201210302819.4A Expired - Fee Related CN102973946B (en) | 2003-07-19 | 2004-07-19 | Compositions comprising components coated with a liquid impermeable but gas permeable layer |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN 200480020770 Pending CN1826102A (en) | 2003-07-19 | 2004-07-19 | Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases |
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| Country | Link |
|---|---|
| JP (1) | JP2012167103A (en) |
| CN (2) | CN1826102A (en) |
| DK (1) | DK1656120T3 (en) |
| EA (1) | EA011854B1 (en) |
| ES (1) | ES2399269T3 (en) |
| GB (2) | GB0316940D0 (en) |
| IL (1) | IL173227A (en) |
| NZ (1) | NZ545365A (en) |
| PT (1) | PT1656120E (en) |
| ZA (1) | ZA200601414B (en) |
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| CN102198119A (en) * | 2011-05-27 | 2011-09-28 | 翟建鹏 | Externally-applied medicinal patch |
| AU2013209343B1 (en) | 2013-05-14 | 2014-04-24 | Activesignal Holding Limited | Device for the Treatment of Bone Conditions |
| CN103599093B (en) * | 2013-11-18 | 2016-06-01 | 中国医学科学院生物医学工程研究所 | A kind of anti-HPV pharmaceutical preparation and purposes |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2119244A (en) * | 1982-04-30 | 1983-11-16 | Alza Corp | Potassium replacement therapy |
| US4970081A (en) * | 1989-01-03 | 1990-11-13 | Sterling Drug Inc. | Controlled-release, low-dose aspirin formulation and method of treating vascular occlusive disease therewith |
| US20010042932A1 (en) * | 1995-07-21 | 2001-11-22 | Edith Mathiowitz | Process for preparing microparticles through phase inversion phenomena |
| WO2003005995A1 (en) * | 2001-07-10 | 2003-01-23 | Aeropharm Technology Incorporated | Core formulation comprising pioglitazone hydrochloride and a biguanide |
-
2003
- 2003-07-19 GB GB0316940A patent/GB0316940D0/en not_active Ceased
- 2003-11-20 GB GB0327006A patent/GB0327006D0/en not_active Ceased
-
2004
- 2004-07-19 NZ NZ545365A patent/NZ545365A/en not_active IP Right Cessation
- 2004-07-19 EA EA200600269A patent/EA011854B1/en not_active IP Right Cessation
- 2004-07-19 CN CN 200480020770 patent/CN1826102A/en active Pending
- 2004-07-19 DK DK04743442.8T patent/DK1656120T3/en active
- 2004-07-19 PT PT47434428T patent/PT1656120E/en unknown
- 2004-07-19 ES ES04743442T patent/ES2399269T3/en active Active
- 2004-07-19 CN CN201210302819.4A patent/CN102973946B/en not_active Expired - Fee Related
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2006
- 2006-01-18 IL IL173227A patent/IL173227A/en not_active IP Right Cessation
- 2006-02-17 ZA ZA200601414A patent/ZA200601414B/en unknown
-
2012
- 2012-04-20 JP JP2012096514A patent/JP2012167103A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2119244A (en) * | 1982-04-30 | 1983-11-16 | Alza Corp | Potassium replacement therapy |
| US4970081A (en) * | 1989-01-03 | 1990-11-13 | Sterling Drug Inc. | Controlled-release, low-dose aspirin formulation and method of treating vascular occlusive disease therewith |
| US20010042932A1 (en) * | 1995-07-21 | 2001-11-22 | Edith Mathiowitz | Process for preparing microparticles through phase inversion phenomena |
| WO2003005995A1 (en) * | 2001-07-10 | 2003-01-23 | Aeropharm Technology Incorporated | Core formulation comprising pioglitazone hydrochloride and a biguanide |
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| SAITO K等: "Effect of ionic interaction of the entrapping of drug into porous microspheres and drug release characteristics", 《PHARMACEUTICAL SOCIETY OF JAPAN》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EA011854B1 (en) | 2009-06-30 |
| GB0327006D0 (en) | 2003-12-24 |
| IL173227A0 (en) | 2006-06-11 |
| PT1656120E (en) | 2013-02-18 |
| IL173227A (en) | 2013-10-31 |
| NZ545365A (en) | 2009-10-30 |
| CN1826102A (en) | 2006-08-30 |
| CN102973946B (en) | 2015-03-18 |
| ZA200601414B (en) | 2007-04-25 |
| GB0316940D0 (en) | 2003-08-27 |
| DK1656120T3 (en) | 2013-03-11 |
| JP2012167103A (en) | 2012-09-06 |
| EA200600269A1 (en) | 2006-08-25 |
| ES2399269T3 (en) | 2013-03-27 |
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