CN1036119C - Application of cereb in medicine for optic atrophy and its compound prepn - Google Patents
Application of cereb in medicine for optic atrophy and its compound prepn Download PDFInfo
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- CN1036119C CN1036119C CN95104482A CN95104482A CN1036119C CN 1036119 C CN1036119 C CN 1036119C CN 95104482 A CN95104482 A CN 95104482A CN 95104482 A CN95104482 A CN 95104482A CN 1036119 C CN1036119 C CN 1036119C
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- citicoline
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Abstract
The present invention relates to citicoline and a compound preparation thereof which are the powder injection used for injection, produced by freeze-drying technology and using citicoline, inosine, adenosine triphosphate and coenzyme A in the forming proportions of 3 to 7:0.5 to 2:0.1 to 3:0.1 to 2.5 as main raw materials, and the citicoline is the medicine used for treating optic atrophy. The present invention has an outstanding treating effect on treating the optic atrophy, and can be used for treating other neuropathies. The medicine and the compound preparation are the metabolism activating agents for the nervous system, promote the biosynthesis of neurocyte phosphatide matrix, and improve the microcirculatory disturbance of the nervous tissue under an anoxic condition. The present invention is clinically used for treating the symptoms of the concomitant optic atrophy, etc., because of the optic nerve injury caused by various reasons.
Description
It is that primary raw material is used for the treatment of ophthalmology optic nerve illness that the present invention designs with citicoline, particularly optic atrophy disease is had the compound preparation of special curative effect.
Optic atrophy is the most refractory disease in the various illness of ophthalmology, is considered to be irreversible for a long time.Cause the reason of optic atrophy varied, its result all shows as pallor papillae, visual deterioration, constriction of visual field, final blinding.General therapeutic medicine to this disease is hormone and blood vessel dilating trophic nerve medicine clinically, as the injection hormone, and vitamin B1, B2 etc., but curative effect is all undesirable.Also useful operation method implement to stimulate in the hope of recovering its function optic nerve, but does not also obtain positive effect, and the total effective rate of Drug therapy and this disease of operative treatment is about 10%.Therefore, China does not still have good medicine to the optic atrophy disease clinically at present and can use.
Citicoline is that KENNEDY equals to find at first that chemical name was the phonetic heavy stone used as an anchor nucleoside diphosphate of a born of the same parents choline in 1954.Citicoline is a nucleoside derivates, is the agent of brain metabolic activation, can strengthen the function of up property network structure activation system, can reduce the cerebral blood vessel resistance, strengthens big cerebral blood flow, improves the cerebrum blood circulation, promotes the brain matter metabolism.In order to treat the disturbance of consciousness that craniocerebral trauma causes, improve upper and lower limb motor function and apoplexy sequela one side or the two lateral deviation paralysiss of apoplexy subacute stage clinically, the promotion brain function recovers and revives.
The characteristics of optic atrophy disease are that phospholipid, protein metabolism are unusual, the microcirculation disturbance pathological changes.According to the pharmacological action of citicoline, illustrate that it is the crucial intermedium of biosynthesis phospholipid, in being the process of phospholipid, biosynthesis plays a significant role.According to these characteristics, we at first are used for the treatment of optic atrophy with citicoline, and purpose is to improve curative effect than existing medicine, and this incurable disease is treated.
We will be that main part medicine becomes injectable powder through the freeze drying process processing and preparing with the citicoline, and Main Ingredients and Appearance comprises citicoline, inosine, adenosine triphosphate, coenzyme A, and the preparation ratio is 3-7: 0.5-2: 0.1-3: 0.1-2.5.
Therefore, the purpose of this invention is to provide a kind of compound preparation, it is characterized in that containing (by weight) citicoline 3-7, inosine 0.5-2, adenosine triphosphate 0.1-3, coenzyme A 0.1-2.5.
Another object of the present invention provides a kind of compound preparation, it is characterized in that containing (by weight) citicoline 3-7, inosine 0.5-2.
Another object of the present invention provides a kind of compound preparation, it is characterized in that containing (by weight) citicoline 3-7, adenosine triphosphate 0.1-3.
Another object of the present invention provides a kind of compound preparation, it is characterized in that containing (by weight) citicoline 3-7, coenzyme A 0.1-2.5.
In effect experiment, find, the optic nerve system has been played excellent repairing and Nutrition based on the compound preparation of citicoline.Select 30 VISTAR rats for use, measure ischium one tibial nerve motor nerve conduction velocity earlier, contaminated for two weeks with acrylamide 30MG/KG per os then, wait to occur back acroparalysis, after motor nerve conduction velocity obviously slows down, be divided into three groups, that is: matched group, low dosage and high-dose therapy group injection citicoline compound preparation carry out the nerve conduction velocity test, once a day, on every Saturdays day, totally two ten days.Low dose group is 0.2ML/KG, and high dose group is 1ML/KG, and matched group is only given normal saline.Result of the test it is as shown in the table low dose group and high dose group rat nerve conduction velocity all speed than matched group is remarkable:
| The neural speed of not leading that passes of group | Treated 10 days | Treated 20 days | The P value |
| High dose group | 38.07±2.22M/S | 42.58±5.08M/S | P∠0.05 |
| Low dose group | 35.20±2.58M/S | 37.54±2.25M/S | P∠0.05 |
| Matched group | 33.06±2.19M/S | 35.63±17.8M/S | P∠ |
Select 36 WISTAR rats for use, at first measure visual evoked potential; Give whole rats by intraperitoneal injection Carbon bisulfide oil solutions (30MG/KG) then; After treating that visual evoked potential prolongs, be divided into matched group, low dose therapy group and high-dose therapy group; Matched group retrobulbar injection normal saline (0.5ML/KG) then; Low dose group retrobulbar injection citicoline compound preparation 0.2ML/KG, high dose group then is 0.5ML/KG.Measure flash of light after ten days and 20 days in treatment and bring out current potential (FEP) and pattern reversal visual evoked potential (PREP); Experimental result shows, when retrobulbar injection citicoline compound preparation ten days and 20 days, than matched group obvious shortening (P ∠ 0.05) arranged when P1, the N1 of low dosage and high-dose therapy group and P2 ripple are hidden.
More than two result of the tests show that citicoline and compound preparation thereof have therapeutical effect to impaired peripheral nerve and optic nerve, can make neurological functional recovery.In the long poison experiment of animal, give rat with citicoline compound preparation by human agent 25 and 50 times of intramuscular injection, every day 1 time, successive administration 30 days.Administration detects hematology and the blood biochemical of rat and learns every index after 30 days, and main organs is carried out histopathologic examination.The result shows every hematology of administration group rat and blood biochemical is learned index and control rats compares, and does not see notable difference, does not also see the Histological change of administration group Rats Organs and Tissues.Under experiment condition and dosage, the citicoline compound preparation intramuscular injection gives rat and does not see the overt toxicity reaction.
Citicoline compound preparation gives domestic cat by 5 times of human dosage and 25 times of intramuscular injection, observes the variation of cat electrocardiogram, blood pressure, heart rate, respiratory frequency and amplitude of respiration in 4 hours after the administration.After the administration of the cat of administration group as a result in 4 hours every index of These parameters and blank group cat compare, do not see notable difference.Show that under experiment condition and dosage, citicoline compound preparation does not have obvious influence to cat electrocardiogram, blood pressure, heart rate, respiratory frequency and amplitude of respiration.
In clinical research, select optic atrophy case 1500 examples that different reasons cause to impose the retrobulbar injection citicoline compound preparation to suffering from eye, each courses of treatment 25 pin, the next day, inject once.After finish a course of treatment, through bringing out potential measurement, suffer from eye vision and obviously improve, the visual field enlarges, and total effective rate reaches 76%, and in the medicine for treatment of similar disease, curative effect is in the clear ahead status, has filled up a blank in the medical domain.The disease of feeling simply helpless is in the past treated and rehabilitation.
With 11 eyes injections of 7 examples wherein citicoline compound preparation is example: naked vision before and after the treatment
Sick class and curative effect
Model case:
Gold * perfume women 13 first day of the lunar New Years of bright clansman's case number 00017.1983 year patient is confused eye and crosses once, and hereafter vision obviously descends, and the visual field feels narrow and small, but through treating with not ing.Binocular vision 0.25 during first visit, and computerized optometry+0.75DS can not but correct.Each has remained 5 ° (white sighting target 5mm) visual field eyes, and intraocular pressure, C value, light penetrating object, portion butterfly, canalis opticus are made film, laboratory values is all normal.The unisexuality atrophy that optical fundus eyes optic disc is slight, since being admitted to hospital, injection citicoline compound preparation next day of every.Every the injection 5 after, binocular vision return to each 0.8, the visual field is extended to 15-20 °.After being expelled to 10 pins, binocular vision respectively is 1.0, and after the course of treatment was full, vision reached 1.2, and the visual field returns to normal range substantially.
Pei * 70 years old people from North Korea of spring man.The original eyes myopia of this patient astigmatism over 4 years vision descend gradually.Be diagnosed as optic atrophy and invalid through western medical treatment in the locality.The right 1M index of vision during first visit, right 30CM index.Computerized optometry is two-2.00NS-3, and 25CDA32 °, but vision can not correct, 30 °, following 40 °, outer 25 °, last 30 °, interior 30 ° an of left side, outer 30 ° last 20 °, CT, is chemically examined sign and is all belonged to normal range by following 40 ° on the right side, the visual field in.Be diagnosed as infectious unisexuality optic atrophy of eyes and myopia astigmatism.After accepting the citicoline compound preparation injection, the vision right side 0.2 (correcting 0.3), a left side 0.3 (correcting 0.4), the visual field increases 20 °.
Confirm that by a large amount of experimental works citicoline compound preparation has outstanding curative effect to the optic atrophy disease.For strengthening its stability, we adopt lyophilization and aseptic subpackaged production technology that this medicine is made injectable powder, have solved the instability problem of soda acid chemical reaction in the water preparation thus, thereby have strengthened commercialized degree.
Composition: citicoline, inosine, adenosine triphosphate, coenzyme A.
Synthetic ratio: above-mentioned composition is equipped with different ratios according to the optic atrophy disease that different reasons cause,
Be generally 3-7; 0.5-2; 0.1-3; 0.1-2.5.
Production technology: conventional freeze-dried powder and aseptic subpackaged.
Indication: behind the optic neuritis, anterior ischemic optic neuropathy, trauma type, brain tumor are repressive, blue or green
Optic atrophys such as light eye, family's heritability.
Claims (4)
1. a compound preparation is characterized in that containing (by weight) citicoline 3-7, inosine 0.5-2, adenosine triphosphate 0.1-3, coenzyme A 0.1-2.5.
2. a compound preparation is characterized in that containing (by weight) citicoline 3-7, inosine 0.5-2.
3. a compound preparation is characterized in that containing (by weight) citicoline 3-7, adenosine triphosphate 0.1-3.
4. a compound preparation is characterized in that containing (by weight) citicoline 3-7, coenzyme A 0.1-2.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95104482A CN1036119C (en) | 1995-06-28 | 1995-06-28 | Application of cereb in medicine for optic atrophy and its compound prepn |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95104482A CN1036119C (en) | 1995-06-28 | 1995-06-28 | Application of cereb in medicine for optic atrophy and its compound prepn |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1138985A CN1138985A (en) | 1997-01-01 |
| CN1036119C true CN1036119C (en) | 1997-10-15 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN95104482A Expired - Fee Related CN1036119C (en) | 1995-06-28 | 1995-06-28 | Application of cereb in medicine for optic atrophy and its compound prepn |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670640A (en) * | 2012-05-29 | 2012-09-19 | 海南卫康制药(潜山)有限公司 | Acetylglutamine lyophilized powder composition for injection and preparation method thereof |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1032402T3 (en) * | 1997-11-26 | 2004-05-10 | Interneuron Pharma | Citicolin for the treatment of motor neuronal and demyelination disorders |
| CN102018673A (en) * | 2010-12-08 | 2011-04-20 | 山东大学齐鲁医院 | Adenosine triphosphate precursor liposome as well as preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE400276C (en) * | 1922-11-20 | 1924-08-18 | Gabriel Elie Guyetant | Cigarette holder |
| CN1114192A (en) * | 1995-06-06 | 1996-01-03 | 王海雁 | Injection for curing optic atrophy and preparing process thereof |
-
1995
- 1995-06-28 CN CN95104482A patent/CN1036119C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE400276C (en) * | 1922-11-20 | 1924-08-18 | Gabriel Elie Guyetant | Cigarette holder |
| CN1114192A (en) * | 1995-06-06 | 1996-01-03 | 王海雁 | Injection for curing optic atrophy and preparing process thereof |
Non-Patent Citations (1)
| Title |
|---|
| 贵州医药14(3) 1996.7.1 饶芝前 胞二磷碱用于治疗视神经萎缩 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670640A (en) * | 2012-05-29 | 2012-09-19 | 海南卫康制药(潜山)有限公司 | Acetylglutamine lyophilized powder composition for injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1138985A (en) | 1997-01-01 |
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