CN1141145C - Medicine for treating thyroidism accompanied by infiltrative exorbitism - Google Patents
Medicine for treating thyroidism accompanied by infiltrative exorbitism Download PDFInfo
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- CN1141145C CN1141145C CNB001000829A CN00100082A CN1141145C CN 1141145 C CN1141145 C CN 1141145C CN B001000829 A CNB001000829 A CN B001000829A CN 00100082 A CN00100082 A CN 00100082A CN 1141145 C CN1141145 C CN 1141145C
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- technetium
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Abstract
The present invention provides a phosphonate medicine of technetium [[99]<Tc>] for treating a hyperthyroidism accompanied by infiltrative exophthalmos. The main effective components of the present invention are the technetium [[99]<Tc>] and the phosphonate. The positive heptavalent technetium of the high technetium [[99]<Tc>] acid sodium is reduced to the positive tetravalent technetium by a reducing agent in the condition of the reducing agent is accepted pharmaceutically, the positive tetravalent technetium reacts with the phosphonic acid to generate a complex compound of technetium [[99]<Tc>] phosphonate. The phosphonate is methylene diphosphonate or hydroxymethylene diphosphonate or ethylenediamine tetramethylene phosphonate or diethylene triamine pentamethylene phosphonate, each unit of the medicine contains 0.04 mug to 2.0 mug of the technetium [[99]<Tc>] and 3 mg to 300 mg of the phosphonate (measured by phosphonic acid content). The present invention has the advantages of less toxic and side effect, short course of treatment, good curative effect, etc.
Description
The present invention relates to a kind of application of medicine, be specifically related to technetium [
99Tc] application of phosphonate medicine in the medicine of preparation treatment thyroidism accompanied by infiltrative exorbitism.
Thyroidism accompanied by infiltrative exorbitism (Graves ' oculopathy) closely related with hyperthyroidism, be a kind of endocrinopathy and autoimmune disease.Think that at present there is the antigen total with parathyroid tissue in socket of the eye inner tissue, these antigenic stimulus lymphocytes produce a large amount of antibody, these antibody comprise TRAb (serum thyrotropin receptor antibody), MCA (thyroid microsomal antibody) and TGA (thyroglobulin antibody) etc., these antibody and antigen form antigen antibody complex, in the presence of complement, make a large amount of T lymphocytic infiltration in the eye socket, the interior fibrocyte of T LS socket of the eye discharges various cytokines and (is mainly TNF-a2, IL-1, INF-γ etc.), oxygen-derived free radicals, and fibroblast growth factor, impel cell regeneration and Glucoamino glucosan (GAGS) synthetic, thereby cause collagen gathering in the socket of the eye, connective tissue increases, the eye muscle plumpness, orbital contents is increased, and produce a series of sings and symptomses, be i.e. thyroidism accompanied by infiltrative exorbitism.This sick sickness rate is higher, and in hyperthyroidism disease, the patient of nearly 13%-45% is a thyroidism accompanied by infiltrative exorbitism, and this disease not only influences patient's outward appearance, and has a strong impact on patient's life.The method of treatment thyroidism accompanied by infiltrative exorbitism is a lot of at present, but none method had both had good effect, and the little characteristics of toxic and side effects, has big side effect as orbital decompression, the outer radiotherapy produce effects of eye socket is slower, after generally wanting the several months positive effect is arranged, and often need to merge immunosuppressant therapy, though immunosuppressant therapy can alleviate the pain that soft tissue inflammation causes rapidly, congested, edema, and can partly improve expophthalmos and ophthalmoplegia and vision, but toxic and side effects is bigger, obviously increases as the thyroidism accompanied by infiltrative exorbitism weight in patients through the immune formulation treatment, central obesity occurs, alopecia also appears in the patient who has, feel sick, multiple toxic and side effects such as insomnia.Additive method is as plasma exchange, immunoglobulin therapy, cytokine therapy etc., because curative effect is not certainly, not by wide clinical application.Therefore development treatment thyroidism accompanied by infiltrative exorbitism good effect, medicine that toxic and side effects is little are very important.
The purpose of this invention is to provide a kind of better efficacy, application technetium that toxic and side effects is little [
99Tc] method of phosphonate medication preparation treatment thyroidism accompanied by infiltrative exorbitism medicine
Technetium provided by the invention [
99Tc] application process of phosphonate medicine in the medicine of preparation treatment thyroidism accompanied by infiltrative exorbitism, its concrete technical scheme is: with high technetium [
99Tc] the phosphonic at least a active ingredients that are such as sour sodium and methylenediphosphonate (MDP), hydroxyl methylenediphosphonate (HMDP), ethylenediamine tetraacetic methylene phosphonic acid (EDTMP), second two support triamine penta-methylene phosphonic acids (DTPMP), under the reducing condition that pharmacopedics allows, be prepared into the technetium that is used for the treatment of thyroidism accompanied by infiltrative exorbitism [
99Tc] the phosphonate medicine, technetium wherein [
99Tc] can for
99The Mo decay obtains
99mThe decay constant of Tc, its content of per unit medicine is (with technetium
99Tc] the content meter) be 0.04 μ g～2.0 μ g, phosphonate content (in phosphonic acids content) is 3mg-300mg.The Reducing agent that allows in the said pharmacy is stannous chloride or stannous fluoride or thiourea dioxide, and its content is 0.3mg～1.0mg in the per unit medicine.In addition for improve technetium [
99Tc] stability of phosphonate, can use antioxidant, as ascorbic acid (vitamin C), its content is 0.2mg～1.0mg, or gentisic acid, its content is 0.2mg～1.0mg.
The present invention according to technetium [
99Tc] phosphonate can remove free radical in the human body, the vigor of superoxide dismutase (SOD) in the protection human body suppresses immune complex and forms, the principle of mediator's body immunity function, utilize technetium [
99Tc] phosphonate treatment endocrine and autoimmune disease---thyroidism accompanied by infiltrative exorbitism, result of the test is found among the thyroidism accompanied by infiltrative exorbitism patient, 85% above patient's serum thyrotropin receptor antibody (TRAb) contents level obviously reduces, patient's sings and symptoms (soft tissue inflammation, ocular movement are limited, visual deterioration, eye bulging etc.) all be improved significantly, illustrate technetium [
99Tc] phosphonate is by regulating the immunologic function of human body, particularly suppressing the generation of serum thyrotropin receptor antibody (TRAb) and treat thyroidism accompanied by infiltrative exorbitism.Little with this type of Drug therapy thyroidism accompanied by infiltrative exorbitism toxic and side effects, short treating period (30-60 days), good effect (effective percentage is up to more than 85%), and treatment is simple, need not be in hospital, and the patient takes like a shot.Therefore, the present invention use technetium [
99Tc] medicine of phosphonate medication preparation treatment thyroidism accompanied by infiltrative exorbitism has obvious superiority and important clinical application value than the medicine of conventional therapy thyroidism accompanied by infiltrative exorbitism.
Specific embodiments of the present invention is as follows:
Technetium [
99Tc] phosphonate can be divided into intravenous fluid and intravenous drip liquid, phosphonic acids content can be 3mg in the per unit medicine (for example 5ml intravenous fluid), 5mg or 10mg, at this moment, phosphonate for above-mentioned every kind of phosphonic acids content, the content of technetium can be 0.04 μ g, 0.05 μ g, 0.07 μ g or 0.10 μ g, the content of stannous chloride or stannous fluoride or thiourea dioxide can be 0.3mg or 0.5mg: phosphonic acids content can be 50mg in the per unit medicine (for example intravenous drip liquid freeze dried powder), 75mg, 100mg, 200mg or 300mg, at this moment, phosphonate for above-mentioned every kind of phosphonic acids content, the content of technetium can be 0.3 μ g, 0.5 μ g, 1 μ g or 2 μ g, the content of stannous chloride or stannous fluoride or thiourea dioxide can be 0.5mg, 0.6mg or 1.0mg.
In above-mentioned various drug types, can also add antioxidants ascorbic acid or gentisic acid, its content can be 0.2mg～1.0mg, and wherein 0.2mg, 0.3mg, 0.4mg, 0.5mg, 0.6mg, 0.7mg, 0.8mg, 0.9mg, 1.0mg are operable dosage.
Optimum implementation of the present invention sees Table 1.
The curative effect of medication of technetiummethylenediphosphonate sees Table 2, table 3, and the curative effect of all the other phosphonates is identical with it.
The concrete preparation method of medicine of the present invention is:
Technetium [
99Tc] preparation of phosphonate intravenous fluid
In clean room, by the sterile working, take by weighing aequum high technetium [
99Tc] sour sodium solid, be dissolved in the normal saline, be diluted to desired concn (with technetium [
99Tc] the content meter), filter with biofilter the back, divides the 7ml glass bottle (liquor capacity is 5ml) of packing into, gland seal, the autoclave sterilization sterilization, be prepared into high technetium [
99Tc] sour sodium injection (A agent); Other takes by weighing the phosphonic acids of aequum, uses the second distillation water dissolution, takes by weighing the stannous chloride (SnCl of aequum again
2.2H
2O), after the dissolving of 1～2ml concentrated hydrochloric acid, an amount of dilute hydrochloric acid of reuse (2N) dilution, and join in the above-mentioned phosphonic acids solution, it is 5.0～7.0 that the back makes pH value with 2N sodium hydroxide solution regulator solution acidity.The back is diluted to desired concn with normal saline, filters with biofilter, divides to install to (every bottle of 1ml) in the 5ml vial again, after lyophilizing, gland seal is prepared into inferior stannum phosphonate lyophilized injectable powder (B agent).Face with preceding by sterile working's requirement, the B agent injected in the A agent, fully vibration reaction, generate technetium [
99Tc] injection of phosphonate complex posterior vein.
Technetium [
99Tc] preparation of phosphonate intravenous drip liquid
In clean room, by sterile working's requirement, take by weighing the phosphonic acids of aequum and high technetium [
99Tc] sour sodium, use the second distillation water dissolution, take by weighing the stannous chloride (SnCl of aequum again
2.2H
2O), with the dissolving of 1～2ml concentrated hydrochloric acid,, mix with above-mentioned phosphonic acids solution again with an amount of dilute hydrochloric acid (2N) dilution, be diluted to desired concn with normal saline, filter with biofilter, divide again and install in the 10ml vial (every bottle of 2ml～2.5ml), lyophilizing, gland seal, make technetium phosphonate intravenous drip liquid injectable powder, during clinical practice, with 250ml～500ml physiological saline solution dilution, intravenous drip (3～4 hours).
" aequum " can refer to the consumption of optimum implementation in the table 1 in the above-mentioned preparation method.Table 1 optimum implementation
* the freeze dried powder of intravenous drip liquid faces with after the preceding 250ml of usefulness respectively, the dilution of 500ml physiological saline solution quiet dripping off more than 3 hours.Antibody horizontal before and after the table 2 treatment thyroidism accompanied by infiltrative exorbitism
Before TRAb (serum thyrotropin receptor antibody) MCA (thyroid microsomal antibody) TGA (thyroglobulin antibody) table 3 treatment and behind the begin treatment April eye situation relatively
Swollen or the swelling 3 severes 4 eyelid erythema of 3 water for washing the faces of pain 2 moderates when * estimating behind 0 asymptomatic and sign 1 ball slight 2 ocular movements of pain and squeezing sense 1 according to NOSPECS standard * * level of activity
| Technetium [ 99Tc] the phosphonate title | Intravenous fluid (5ml) phosphonic acids technetium [ 99Tc] stannous chloride (mg) (μ g) is (mg) | Intravenous drip liquid (freeze dried powder) phosphonic acids technetium [ 99Tc] stannous chloride (mg) (μ g) is (mg) |
| Technetium [ 99Tc] methylene diphosphonate | 5 0.05 0.5 10 0.10 0.5 | 100 0.3 0.6 200 0.5 1.0 |
| Technetium [ 99Tc] the hydroxyl methylene diphosphonate | 5 0.05 0.5 10 0.10 0.5 | 50 0.3 0.6 100 0.5 1.0 |
| Technetium [ 99Tc] ethylenediamine tetraacetic methylene phosphonic acid salt | 5 0.05 0.5 10 0.10 0.5 | 75 0.3 0.6 150 0.5 1.0 |
| Technetium [ 99Tc] diethylene triamine pentamethylene phosphonic acid salt | 5 0.05 0.5 10 0.10 0.5 | 75 0.3 0.6 150 0.5 1.0 |
| Case | TRAb(U/L) | MCA(％) | TGA(％) |
| Front and back | Front and back | Front and back | |
| 1 2 3 4 5 6 7 8 9 10 11 | 102.3 22.8 98.8 12.6 47.8 10.2 90.7 10.5 84.7 22.6 51.2 19.5 123.8 32.6 104.5 23.1 55.6 10.6 57.5 16.3 101.2 21.3 | 25.2 10.3 21.4 12.3 17.9 17.4 46.2 28.3 3.9 3.1 24.7 13.5 24.7 23.3 35.2 14.3 46.3 28.2 27.9 18.9 32.1 12.1 | 33.4 20.9 34.7 14.3 10.2 9.6 50.4 32.2 5.1 4.9 33.2 22.3 35.6 34.1 44.7 24.9 55.4 22.5 31.2 19.1 42.0 22.1 |
| Case | Soft tissue inflammation * | Eye bulging (mm) | Ocular motility disorder * | Inpairment of vision * | The active * * of GO | Oculopathy index * * * | The course of disease (moon) |
| Front and back | Front and back | Front and back | Front and back | Front and back | Front and back | ||
| 1 2 3 4 5 6 7 8 9 10 11 | 3 0 2 0 0 0 2 0 2 0 1 1 2 0 3 0 2 0 3 1 3 0 | 20 19 21 20 23 22 22 20 20 19 22 21 19 19 23 22 23 22 26 24 20 19 | 0 0 1 0 1 0 2 1 0 0 0 0 0 0 2 0 1 0 2 0 0 0 | 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 | 7 0 6 0 0 0 4 0 0 0 2 2 4 0 6 0 4 0 6 1 7 0 | 4 1 4 1 3 1 7 3 3 1 3 2 3 1 7 2 5 2 8 3 4 1 | 6 5 8 4 7 9 12 8 4 6 5 |
5 conjunctival congestions
6 chemosiss
Abundant swelling * * * oculopathy index is 1 minute according to each bar more than the NOSPECS staging in 7, and addition promptly gets standard, with the numerical value addition at different levels promptly.The active total points of GO.
Claims (4)
- A technetium [ 99Tc] application of phosphonate medicine in the medicine of preparation treatment thyroidism accompanied by infiltrative exorbitism, it is characterized in that: application process is in the presence of the Reducing agent that allows in pharmacopedics, high technetium [ 99Tc] positive septivalency technetium in the sour sodium is reduced into positive tetravalence technetium, with phosphonic acids generate technetium [ 99Tc] the phosphonate complex, make the medicine for the treatment of thyroidism accompanied by infiltrative exorbitism, technetium in the per unit medicine [ 99Tc] content be 0.04 μ g～2.0 μ g, phosphonate content (in phosphonic acids content) is 3mg～300mg.
- Technetium 2. as claimed in claim 1 [ 99Tc] application of phosphonate medicine in the medicine of preparation treatment thyroidism accompanied by infiltrative exorbitism, it is characterized in that: the Reducing agent that allows in the said pharmacopedics is stannous chloride or stannous fluoride or thiourea dioxide, its content is 0.3mg～1.0mg in the per unit medicine.
- Technetium 3. as claimed in claim 1 [ 99Tc] application of phosphonate medicine in the medicine of preparation treatment thyroidism accompanied by infiltrative exorbitism, it is characterized in that: use technetium [ 99Tc] contain antioxidants ascorbic acid or gentisic acid in the treatment thyroidism accompanied by infiltrative exorbitism medicine of phosphonate medication preparation, its content is 0.2mg～1.0mg in the per unit medicine.
- Technetium 4. as claimed in claim 2 [ 99Tc] application of phosphonate medicine in the medicine of preparation treatment thyroidism accompanied by infiltrative exorbitism, it is characterized in that: use technetium [ 99Tc] contain antioxidants ascorbic acid or gentisic acid in the treatment thyroidism accompanied by infiltrative exorbitism medicine of phosphonate medication preparation, its content is 0.2mg～1.0mg in the per unit medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001000829A CN1141145C (en) | 2000-01-06 | 2000-01-06 | Medicine for treating thyroidism accompanied by infiltrative exorbitism |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001000829A CN1141145C (en) | 2000-01-06 | 2000-01-06 | Medicine for treating thyroidism accompanied by infiltrative exorbitism |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1302665A CN1302665A (en) | 2001-07-11 |
| CN1141145C true CN1141145C (en) | 2004-03-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB001000829A Expired - Fee Related CN1141145C (en) | 2000-01-06 | 2000-01-06 | Medicine for treating thyroidism accompanied by infiltrative exorbitism |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103203032B (en) * | 2012-01-12 | 2017-05-17 | 成都云克药业有限责任公司 | Technetium [99Tc] methylenediphosphonate preparation and preparation method thereof |
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2000
- 2000-01-06 CN CNB001000829A patent/CN1141145C/en not_active Expired - Fee Related
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| CN1302665A (en) | 2001-07-11 |
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